Secreted and transmembrane polypeptides and nucleic acids encoding the same

ABSTRACT

The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

FIELD OF THE INVENTION

[0001] The present invention relates generally to the identification andisolation of novel DNA and to the recombinant production of novelpolypeptides.

BACKGROUND OF THE INVENTION

[0002] Extracellular proteins play important roles in, among otherthings, the formation, differentiation and maintenance of multicellularorganisms. The fate of many individual cells, e.g., proliferation,migration, differentiation, or interaction with other cells, istypically governed by information received from other cells and/or theimmediate environment. This information is often transmitted by secretedpolypeptides (for instance, mitogenic factors, survival factors,cytotoxic factors, differentiation factors, neuropeptides, and hormones)which are, in turn, received and interpreted by diverse cell receptorsor membrane-bound proteins. These secreted polypeptides or signalingmolecules normally pass through the cellular secretory pathway to reachtheir site of action in the extracellular environment.

[0003] Secreted proteins have various industrial applications, includingas pharmaceuticals, diagnostics, biosensors and bioreactors. Mostprotein drugs available at present, such as thrombolytic agents,interferons, interleukins, erythropoietins, colony stimulating factors,and various other cytokines, are secretory proteins. Their receptors,which are membrane proteins, also have potential as therapeutic ordiagnostic agents. Efforts are being undertaken by both industry andacademia to identify new, native secreted proteins. Many efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. Examples ofscreening methods and techniques are described in the literature [see,for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996);U.S. Pat. No. 5,536,637)].

[0004] Membrane-bound proteins and receptors can play important rolesin, among other things, the formation, differentiation and maintenanceof multicellular organisms. The fate of many individual cells, e. g.,proliferation, migration, differentiation, or interaction with othercells, is typically governed by information received from other cellsand/or the immediate environment. This information is often transmittedby secreted polypeptides (for instance, mitogenic factors, survivalfactors, cytotoxic factors, differentiation factors, neuropeptides, andhormones) which are, in turn, received and interpreted by diverse cellreceptors or membrane-bound proteins. Such membrane-bound proteins andcell receptors include, but are not limited to, cytokine receptors,receptor kinases, receptor phosphatases, receptors involved in cell-cellinteractions, and cellular adhesin molecules like selectins andintegrins. For instance, transduction of signals that regulate cellgrowth and differentiation is regulated in part by phosphorylation ofvarious cellular proteins. Protein tyrosine kinases, enzymes thatcatalyze that process, can also act as growth factor receptors. Examplesinclude fibroblast growth factor receptor and nerve growth factorreceptor.

[0005] Membrane-bound proteins and receptor molecules have variousindustrial applications, including as pharmaceutical and diagnosticagents. Receptor immunoadhesins, for instance, can be employed astherapeutic agents to block receptor-ligand interactions. Themembrane-bound proteins can also be employed for screening of potentialpeptide or small molecule inhibitors of the relevant receptor/ligandinteraction.

[0006] Efforts are being undertaken by both industry and academia toidentify new, native receptor or membrane-bound proteins. Many effortsare focused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel receptor or membrane-boundproteins.

[0007] 1. PRO281

[0008] A novel gene designated testis enhanced gene transcript (TEGT)has recently been identified in humans (Walter et al., Genomics20:301-304 (1995)). Recent results have shown that TEGT protein isdevelopmentally regulated in the mammalian testis and possesses anuclear targeting motif that allows the protein to localize to thenucleus (Walter et al., Mamm. Genome 5:216-221 (1994)). As such, it isbelieved that the TEGT protein plays an important role in testisdevelopment. There is, therefore, substantial interest in identifyingand characterizing novel polypeptides having homology to the TEGTprotein. We herein describe the identification and characterization ofnovel polypeptides having homology to TEGT protein, designated herein asPRO281 polypeptides.

[0009] 2. PRO276

[0010] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentity the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO276 polypeptides.

[0011] 3. PRO189

[0012] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO189 polypeptides.

[0013] 4. PRO190

[0014] Of particular interest are proteins having seven transmembranedomains (7TM), or more generally, all multiple transmembrane spanningproteins. Among multiple transmembrane spanning proteins are ionchannels and transporters. Examples of transporters are theUDP-galactose transporter described in Ishida, et al., J. Biochem.,120(6): 1074-1078 (1996), and the CMP-sialic acid transporter describedin Eckhardt, et al., PNAS, 93(15):7572-7576 (1996). We herein describethe identification and characterization of novel transmembranepolypeptides, designated herein as PRO190 polypeptides.

[0015] 5. PRO341

[0016] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO341 polypeptides.

[0017] 6. PRO180

[0018] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO180 polypeptides.

[0019] 7. PRO194

[0020] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO194 polypeptides.

[0021] 8. PRO203

[0022] Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. ATPases are a family of enzymesthat play a variety of important roles, including energizing transportof ions and molecules, across cellular membranes. Transport mechanismsthat employ ATPases often involve excluding xeno- and endobiotic toxinsfrom the cellular environment, thereby protecting cells from toxicity ofthese compounds. Lu et al. report a detoxification mechanism whereglutathione S-transferase (GST) catalyzes glutathionation of planttoxins, and a specific Mg²⁺-ATPase is involved in the transport of theglutathione S-conjugates from the cytosol. Proc. Natl. Acad. Sci. USA94(15):8243-8248 (1997). This study and others indicate the importanceof the identification of ATPases, such as GST ATPases, and of novelproteins having sequence identity with ATPases.

[0023] More generally, and also of interest are novel membrane-boundproteins, including those which may be involved in the transport of ionsand molecules across membranes. Membrane-bound proteins and receptorscan play an important role in the formation, differentiation andmaintenance of multicellular organisms. The fate of many individualcells, e.g., proliferation, migration, differentiation, or interactionwith other cells, is typically governed by information received fromother cells and/or the immediate environment. This information is oftentransmitted by secreted polypeptides (for instance, mitogenic factors,survival factors, cytotoxic factors, differentiation factors,neuropeptides, and hormones) which are, in turn, received andinterpreted by diverse cell receptors or membrane-bound proteins. Suchmembrane-bound proteins and cell receptors include, but are not limitedto, cytokine receptors, receptor kinases, receptor phosphatases,receptors involved in cell-cell interactions, and cellular adhesinmolecules like selectins and integrins. For instance, transduction ofsignals that regulate cell growth and differentiation is regulated inpart by phosphorylation of various cellular proteins. Protein tyrosinekinases, enzymes that catalyze that process, can also act as growthfactor receptors. Examples include fibroblast growth factor receptor andnerve growth factor receptor.

[0024] In light of the important physiological roles played by ATPasesand membrane-bound proteins efforts are being undertaken by bothindustry and academia to identify new, native membrane-bound proteins,and proteins having sequence identity to ATPases. We herein describe theidentification and characterization of novel polypeptides havingsequence identity to GST ATPase, designated herein as PRO203polypeptides.

[0025] 9. PRO290

[0026] Of particular interest are novel proteins and nucleic acids whichhave sequence identity with known proteins and nucleic acids. Proteinsof interest which are well known in the art include NTII-1, a nerveprotein which facilitates regeneration, FAN, and beige. Beige, or bg, isa murine analog related to Chediak-Higashi Syndrome (CHS), a rareautosomal recessive disease in which neutrophils, monocytes andlymphocytes contain giant cytoplasmic granules. See Perou et al., J.Biol. Chem. 272(47):29790 (1997) and Barbosa et al., Nature 382:262(1996).

[0027] We herein describe the identification and characterization ofnovel polypeptides having sequence identity to NTII-1, FAN and beige,designated herein as PRO290 polypeptides.

[0028] 10. PRO874

[0029] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO194 polypeptides.

[0030] 11. PRO710

[0031] In Saccharomyces cerevisiae, the chromatin structure of DNAreplication origins changes as cells become competent for DNAreplication, suggesting that G1 phase-specific association ofreplication factors with origin DNA regulates entry into S phase(Aparicio et al., Cell 91:59-69 (1997)). In fact, it has been shown thatthe initiation of DNA replication in Saccharomyces cerevisiae requiresthe protein product of the CDC45 gene which encodes a protein that staysat relatively constant levels throughout the cell cycle (Owens et al.,Proc. Natl. Acad. Sci USA 94:12521-12526 (1997)). The CDC45 protein ispart of a prereplication complex that may move with DNA replicationforks in yeast. Given the obvious importance of the CDC45 protein in DNAreplication, there is significant interest in identifying andcharacterizing novel polypeptides having homology to CDC45. We hereindescribe the identification and characterization of novel polypeptideshaving homology to the CDC45 protein, designated herein as PRO710polypeptides.

[0032] 12. PRO1151

[0033] The complement proteins comprise a large group of serum proteinssome of which act in an enzymatic cascade, producing effector moleculesinvolved in inflammation. The complement proteins are of particularimportance in regulating movement and function of cells involved ininflammation. One of the complement proteins, C1q, has been shown to beinvolved in the recognition of microbial surfaces and antibody-antigencomplexes in the classical pathway of complement (Shapiro et al., Curr.Biol. 8(6):335-338 (1998)).

[0034] Given the physiological importance of inflammation and relatedmechanisms in vivo and in the specific physiological activities ofcomplement C1q protein, efforts are currently being undertaken toidentify new, native proteins which share sequence similarity to thecomplement proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to complement C1qprotein, designated herein as PRO1151 polypeptides.

[0035] 13. PRO1282

[0036] All proteins containing leucine-rich repeats are thought to beinvolved in protein-protein interactions. Leucine-rich repeats are shortsequence motifs present in a number of proteins with diverse functionsand cellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415-421 (October 1994); Kobe and Deisenhofer,Curr. Opin. Struct. Biol., 5(3):409-416 (1995).

[0037] A study has been reported on leucine-rich proteoglycans whichserve as tissue organizers, orienting and ordering collagen fibrilsduring ontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141-174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215-222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bernard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO91/0727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factorβ hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

[0038] Another protein which has been reported to have leucine-richrepeats is the SLIT protein which has been reported to be useful intreating neuro-degenerative diseases such as Alzheimer's disease, nervedamage such as in Parlinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO92/0518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland),125(1-2):65-70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.,6(4): 1125-1133 (October 1995) (kidney disease involvement).

[0039] Leucine rich repeat proteins are further discussed in Kajava, J.Mol. Biol., 277(3):519-527 (1998), Nagasawa, et al., Genomics,44(3):273-279 (1997), Bengtsson, J. Biol. Chem., 270(43):25639-25644(1995), Gaillard, et al., Cell, 65(7):1127-1141 (1991) and Ohkura andYanagida, Cell, 64(1):149-157 (1991), all incorporated herein byreference.

[0040] Thus, due to all the reasons listed above, new members of theleucine rich repeat superfamily are of interest. On a more generallevel, all novel proteins are of interest. We herein describe theidentification and characterization of novel leucine-richrepeat-containing polypeptides, designated herein as PRO1282polypeptides.

[0041] 14. PRO358

[0042] The cloning of the Toll gene of Drosophila, a maternal effectgene that plays a central role in the establishment of the embryonicdorsal-ventral pattern, has been reported by Hashimoto et al., Cell52:269-279 (1988). The Drosophila Toll gene encodes an integral membraneprotein with an extracytoplasmic domain of 803 amino acids and acytoplasmic domain of 269 amino acids. The extracytoplasmic domain has apotential membrane-spanning segment, and contains multiple copies of aleucine-rich segment, a structural motif found in many transmembraneproteins. The Toll protein controls dorsal-ventral patterning inDrosophila embryos and activates the transcription factor Dorsal uponbinding to its ligand Spätzle. (Morisato and Anderson, Cell 76:677-688(1994)). In adult Drosophila, the Toll/Dorsal signaling pathwayparticipates in the anti-fungal immune response. (Lenaitre et al., Cell86:973-983 (1996)).

[0043] A human homologue of the Drosophila Toll protein has beendescribed by Medzhitov et al., Nature 388:394-397 (1997). This humanToll, just as Drosophila Toll, is a type I transmembrane protein, withan extracellular domain consisting of 21 tandemly repeated leucine-richmotifs (leucine-rich region—LRR), separated by a non-LRR region, and acytoplasmic domain homologous to the cytoplasmic domain of the humaninterleukin-1 (IL-1) receptor. A constitutively active mutant of thehuman Toll transfected into human cell lines was shown to be able toinduce the activation of NF-κB and the expression of NF-κB-controlledgenes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as theexpression of the constimulatory molecule B7.1, which is required forthe activation of native T cells. It has been suggested that Tollfunctions in vertebrates as a non-clonal receptor of the immune system,which can induce signals for activating both an innate and an adaptiveimmune response in vertebrates. The human Toll gene reported byMedzhitov et al., supra was most strongly expressed in spleen andperipheral blood leukocytes (PBL), and the authors suggested that itsexpression in other tissues may be due to the presence of macrophagesand dendritic cells, in which it could act as an early-warning systemfor infection. The public GenBank database contains the following Tollsequences: Toll1 (DNAX# HSU88540-1, which is identical with the randomsequenced full-length cDNA #HUMRSC786-1); Toll2 (DNAX# HSU88878-1);Toll3 (DNAX# HSU88879-1); and Toll4 (DNAX# HSU88880-1, which isidentical with the DNA sequence reported by Medzhitov et al., supra). Apartial Toll sequence (Toll5) is available from GenBank under DNAX#HSU88881-1.

[0044] Further human homologues of the Drosophila Toll protein,designated as Toll-like receptors (huTLRs1-5) were recently cloned andshown to mirror the topographic structure of the Drosophila counterpart(Rocket al., Proc. Natl. Acad. Sci. USA 95:588-593 [1998]).Overexpression of a constitutively active mutant of one human TLR(Toll-protein homologue—Medzhitov et al., supra; TLR4—Rock et al.,supra) leads to the activation of NF-κB and induction of theinflammatory cytokines and constimulatory molecules. Medzhitov et al.,supra.

[0045] We herein describe the identification and characterization ofnovel polypeptides having homology to Toll, designated herein as PRO358polypeptides.

[0046] 15. PRO1310

[0047] Of interest are proteins related to carboxypeptidases. Variouscarboxypeptidases are described in the literature, i.e., Krause et al.,Immunol. Rev. 161:119-127 (1998) and Leiter, J. Endocrinol.155(2):211-214 (1997). We herein describe the identification andcharacterization of novel polypeptides having homology to acarboxypeptidase, designated herein as PRO1310 polypeptides.

[0048] 16. PRO698

[0049] The extracellular mucous matrix of olfactory neuroepithelium is ahighly organized structure in intimate contact with chemosensory ciliathat house the olfactory transduction machinery. The major proteincomponent of this extracellular matrix is olfactomedin, a glycoproteinthat is expressed in olfactory neuroepithelium and which formintermolecular disulfide bonds so as to produce a polymer (Yokoe et al.,Proc. Natl. Acad. Sci. USA 90:46554659 (1993), Bal et al., Biochemistry32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153(1991)). It has been suggested that olfactomedin may influence themaintenance, growth or differentiation of chemosensory cilia on theapical dendrites of olfactory neurons. Given this important role, thereis significant interest in identifying and characterizing novelpolypeptides having homology to olfactomedin. We herein describe theidentification and characterization of novel polypeptides havinghomology to olfactomedin protein, designated herein as PRO698polypeptides.

[0050] 17. PRO732

[0051] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides having sequence identity to the Diff33protein, designated herein as PRO732 polypeptides.

[0052] 18. PRO1120

[0053] Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Sulfatases are a family of secretedenzymatic proteins that play a variety of important metabolic roles andthus are the subject of interest in research and industry (see, e.g.,Sleat et al., Biochem J., 324(Pt. 1):33-39 (1997)). Deficiencies ofcertain sulfatases have been implicated in various human disordersincluding Sanfilippo D syndrome (see, Litjens et al., Biochem J. 327(Pt1):899-94 (1997); Leipprandtet al. J. Inherit Metab. Dis. 18(5):647-648(1995); and Freemanet al. Biochem J. 282(pt2):605-614 (1992)). We hereindescribe the identification and characterization of novel polypeptideshaving sequence identity to sulfatase protein, designated herein asPRO1120 polypeptides.

[0054] 19. PRO537

[0055] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO537 polypeptides.

[0056] 20. PRO536

[0057] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO536 polypeptides.

[0058] 21. PRO535

[0059] Isomerase proteins play many important physiological roles in themammal. Many different types of isomerase proteins have been identifiedand characterized including, for example, protein disulfide isomerasesand peptidyl-prolyl isomerases. It has been reported that manyimmunophilin proteins, i.e., proteins that serves as receptors forimmunosuppressant drugs, exhibit peptidyl-prolyl isomerase activity inthat they function to catalyze the interconversion of the cis and transisomerase of peptide and protein substrates for immunophilin proteins.As such, there is significant interest in identifying and characterizingnovel polypeptides having sequence similarity to peptidyl-prolylisomerase proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to a putativepeptidyl-prolyl isomerase protein, designated herein as PRO535polypeptides.

[0060] 22. PRO718

[0061] Efforts are being undertaken by both industry and academia toidentify new, native transmembrane proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel transmembrane proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO718 polypeptides.

[0062] 23. PRO872

[0063] Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Dehydrogenases and desaturases area family of enzymes that play a variety of important metabolic roles andthus are the subject of interest in research and industry (see Hable etal., Mol. Gen. Genet. 257(2):167-176 (1998); Schneider, C. et al., Prot.Expr. Purif. 10(2):175-179 (1997)). We herein describe theidentification and characterization of novel polypeptides havingsequence identity to dehydrogenase proteins, designated herein as PRO872polypeptides.

[0064] 24. PRO1063

[0065] Collagens constitute the most abundant proteins of theextracellular matrix (ECM) in mammalian organisms. Collagen and othermacromolecules of the ECM are deposited by resident cells and organizedinto a three-dimensional meshwork. This ECM environment plays anessential role in guiding cell migration and in cell-to-cellcommunication during morphogenic processes. The restructuring of the ECMduring remodeling occurs as a cooperative multistep process involving alocalized degradation of existing macromolecules, rearrangement of thecytoskeleton, cell translocation, and deposition of new ECM components.Involved in this restructuring are enzymes such as collagenases andgelatinases which play important roles in the degradation of the ECM. Inlight of the obviously important roles played by the collagenaseenzymes, there is substantial interest in identifying and characterizingnovel polypeptides having homology to these proteins. We herein describethe identification and characterization of novel polypeptides havinghomology to human type IV collagenase protein, designated herein asPRO1063 polypeptides.

[0066] 25. PRO619

[0067] Immunoglobulins are antibody molecules, the proteins thatfunction both as receptors for antigen on the B-cell membrane and as thesecreted products of the plasma cell. Like all antibody molecules,immunoglobulins perform two major functions: they bind specifically toan antigen and they participate in a limited number of biologicaleffector functions. Therefore, new members of the Ig superfamily arealways of interest.

[0068] Of particular interest are novel gene products associated with muchains in immature B cells. Shirasawa, et al., EMBO J., 12(5):1827-1834(1993); Dul, et al., Eur. J. Immunol., 26(4):906-913 (1996). Moreover,the molecular components and assembly of mu surrogate light chaincomplexes in pre-B cell lines are of interest. Ohnishi and Takemori, J.Biol. Chem., 269(45):28347-28353 (1994); Bauer, et al., Curr. Top.Microbiol., 137:130-135 (1988). Novel nucleic acids and peptides relatedto VpreB1, VpreB2 and VpreB3 by sequence identity are of particularinterest. The assembly and manipulation of immunoglobulins can effectthe entire industry related to antibodies and vaccines.

[0069] We herein describe the identification and characterization ofnovel polypeptides having homology to VpreB proteins, designated hereinas PRO619 polypeptides.

[0070] 26. PRO943

[0071] Fibroblast growth factor (FGF) proteins exhibit a variety ofactivities and act by binding to cell surface fibroblast growth factorreceptors. Many different fibroblast growth factor receptors have beenidentified and characterized, including the fibroblast growth factorreceptor-4, which has been shown to be a high affinity receptor for bothacidic and basic FGF (Ron et al., J. Biol. Chem. 268:5388-5394 (1993)and Stark et al., Development 113:641-651 (1991)). Given the obviousimportance of the FGF family of proteins and the cell surface receptorsto which they bind, there is significant interest in identifying novelpolypeptides having homology to the FGF receptor family. We hereindescribe the identification and characterization of novel polypeptideshaving homology to the fibroblast growth factor receptor-4 protein,designated herein as PRO943 polypeptides.

[0072] 27. PRO1188

[0073] The identification of nucleotide pyrophosphohydrolases has beenof interest because of the potential roles these secreted molecules playin calcium pyrophosphate dihydrate (CPPD) deposition disease, arthritis,and other joint diseases (see Masuda et al. J. Rheumatol. (997)24(8):1588-1594; and Terkeltaub et al., Arthritis Rheum (1998)37(6):934-941). We herein describe the identification andcharacterization of novel polypeptides having homology to nucleotidepyrophosphohydrolases, designated herein as PRO1188 polypeptides.

[0074] 28. PRO1133

[0075] Netrins are molecules that guide growing axons and that arestrikingly similar in sequence and in function in flies, nematodes andvertebrates. Additionally, netrin receptors have been identified in allthree animal groups and shown to have crucial, conserved roles in axonnavigation. Netrins and their receptors are further described in theliterature, i.e., Varela-Echavarria and Guthrie, Genes Dev.,11(5):545-557 (1997); Guthrie, Curr. Biol., 7(1):R6-R9 (1997); andKeynes and Cook, Neuron, 17(6):1031-1034 (1996). Due to their relationto neurons, netrins and their related proteins are of interest. Ofparticular interest are molecules having sequence identity or similaritywith netrin. We herein describe the identification and characterizationof novel polypeptides having homology to netrins, designated herein asPRO1133 polypeptides.

[0076] 29. PRO784

[0077] Of interest are membrane-bound and receptor proteins involved inintracellular signaling, metabolism, transport, and other pathways. Forexample, membrane-bound proteins of the endoplasmic reticulum and golgiapparatus play important roles in the transport of proteins. The sec22protein is an endoplasmic reticulum membrane-bound protein involved infundamental membrane trafficking reactions where secretory products arerouted from their site of synthesis to their final destination. Theroles of sec22 in transport pathways have been reported by numerousinvestigators (see Tang et al., Biochem Biophys Res Commun243(3):885-891 (1998); Hay et al., J. Biol. Chem. 271(10):5671-5679(1996); and Newman et al., Mol. Cell. Biol. 10(7):3405-3414 (1990)). Weherein describe the identification and characterization of novelpolypeptides having homology to sec22, designated herein as PRO784polypeptides.

[0078] 30. PRO783

[0079] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO783 polypeptides.

[0080] 31. PRO820

[0081] Immunoglobulin molecules play roles in many important mammalianphysiological processes. The structure of immunoglobulin molecules hasbeen extensively studied and it has been well documented that intactimmunoglobulins possess distinct domains, one of which is the constantdomain or F_(c) region of the immunoglobulin molecule. The F_(c) domainof an immunoglobulin, while not being directly involved in antigenrecognition and binding, does mediate the ability of the immunoglobulinmolecule, either uncomplexed or complexed with its respective antigen,to bind to F_(c) receptors either circulating in the serum or on thesurface of cells. The ability of an F_(c) domain of an immunoglobulin tobind to an F_(c) receptor molecule results in a variety of importantactivities, including for example, in mounting an immune responseagainst unwanted foreign particles. Thus, molecules related to F_(c)receptors are of interest. F_(c) receptors are further described inTominaga et al., Biochem. Biophys. Res. Commun., 168(2):683-689 (1990);Zhang et al., Immuno., 39(6):423-427 (1994). We herein describe theidentification and characterization of novel polypeptides havinghomology to F_(c) receptor, designated herein as PRO820 polypeptides.

[0082] 32. PRO1080

[0083] The folding of proteins and the assembly of protein complexeswithin subcompartments of the eukaryotic cell is catalysed by differentmembers of the Hsp70 protein family. The chaperone function of Hsp70proteins in these events is regulated by members of the DnaJ-likeprotein family, which occurs through direct interaction of differentHsp70 and DnaJ-like protein pairs that appear to be specifically adaptedto each other. The diversity of functions of DnaJ-like proteins usingspecific examples of DnaJ-Hsp70 interactions with polypeptides in yeastprotein-biogenesis pathways is further described in Cyr et al., TrendsBiochem. Sci., 19(4): 176-181 (1994). DnaJ proteins and theirinvolvement in the binding of secretory precursor polypeptides to atranslocon subcomplex and polypeptide translocation machinery in theyeast endoplasmic reticulum are further described in Lyman and Schekman,Cell 88(1):85-96 (1997) and Lyman and Schekman, Experientia 52(12):1042-1049 (1996), respectively. Thus, DnaJ proteins are of interest, asare proteins related to DnaJ proteins, particularly those havingsequence identity with DnaJ proteins. We herein describe theidentification and characterization of novel polypeptides havinghomology to DnaJ proteins, designated herein as PRO1080 polypeptides.

[0084] 33. PRO1079

[0085] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1079 polypeptides.

[0086] 34. PRO793

[0087] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO793 polypeptides.

[0088] 35. PRO1016

[0089] Enzymatic proteins play important roles in the chemical reactionsinvolved in the digestion of foods, the biosynthesis of macromolecules,the controlled release and utilization of chemical energy, and otherprocesses necessary to sustain life. Acyltransferases are enzymes whichacylate moieties. Acyl-glycerol-phosphate acyltransferases can act onlysophosphatidic acid as a substrate. The lysophosphatidic acid isconverted to phophatidic acid and thus plays a role in formingphosphatidylethanolamine found in membranes. See, Brown, et al., PlantMol. Biol., 26(1):211-223 (1994). Thus, acyltransferases play animportant role in the biosynthesis of molecules requiring acylation. Weherein describe the identification and characterization of novelpolypeptides having homology to acyltransferase proteins, designatedherein as PRO1016 polypeptides.

[0090] 36. PRO1013

[0091] Efforts are being undertaken by both industry and academia toidentify new, native proteins. Many of these efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel proteins. We herein describe the identification andcharacterization of novel polypeptides, designated herein as PRO1013polypeptides.

[0092] 37. PRO937

[0093] The glypican family of heparan sulfate proteoglycans are majorcell-surface proteoglycans of the developing nervous system. It isbelieved that members of the glypican family play a role in regulatingcell cycle progression during the transition of proliferating neuronalprogenitor cells to differentiated neurons. Lander et al. Perspect Dev.Neurobiol 3(4):347-358 (1996). It is likely that proteoglycans of theglypican family play other important roles in neural development (Landeret al., supra), and as well as other tissues, as glypican family membershave also been found in the developing kidney (Watanabe et al. J. CellBiol. 130(5):1207-1218 (1995)). Accordingly, the identification of newmembers of the glypican family of proteins is of interest in researchand in industry.

[0094] Described herein is the identification and characterization ofnovel polypeptides having sequence identity with glypican familyproteins, designated herein as PRO937 polypeptides.

[0095] 38. PRO842

[0096] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO842 polypeptides.

[0097] 39. PRO839

[0098] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO839 polypeptides.

[0099] 40. PRO1180

[0100] Methyltransferase enzymes catalyze the transfer of methyl groupsfrom a donor molecule to an acceptor molecule Methyltransferase enzymesplay extremely important roles in a number of different biologicalprocesses including, for example, in the electron transport chain in theplasma membrane in prokaryotes and in the inner mitochondrial membranein eukaryotic cells (see, e.g., Barkovich et al., J. Biol. Chem.272:9182-9188 (1997), Dibrov et al., J. Biol. Chem. 272:9175-9181(1997), Lee et al., J. Bacteriol. 179:1748-1754 (1997) and Marbois etal., Arch. Biochem. Biophys. 313:83-88 (1994)). Methyltransferaseenzymes have been shown to be essential for the biosynthesis ofubiquinone (coenzyme Q) and menaquinone (vitamin K2), both of which areessential isoprenoid quinone components of the respiratory electrontransport chain. Given the obvious importance of the methyltransferaseenzymes, there is substantial interest in identifying novel polypeptidehomologs of the methyltransferases. We herein describe theidentification and characterization of a novel polypeptide havinghomology to methyltransferase enzymes, designated herein as PRO1180polypeptides.

[0101] 41. PRO1134

[0102] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1134 polypeptides.

[0103] 42. PRO830

[0104] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO830 polypeptides.

[0105] 43. PRO1115

[0106] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1115 polypeptides.

[0107] 44. PRO1277

[0108] Efforts are being undertaken by both industry and academia toidentify new, native proteins. Many efforts are focused on the screeningof mammalian recombinant DNA libraries to identify the coding sequencesfor novel receptor and other proteins. Of interest is the identificationof proteins that may play roles in various human disorders anddysfunction. For example, the identification of proteins of the ear andthe functions they play in hearing may lead to an understanding of thecauses of hearing loss and deafness. Coch-B2 is one such protein thathas been found to be specifically expressed in the inner ear (cochlea).It has been characterized and studied for its possible role in hearingloss (Robertson et al. Genomics (1994) 23(1):52-50; Robertson et al.Genomics (1997) 46(3):345-354). We herein describe the identificationand characterization of novel polypeptides having sequence identity toCoch-B2, designated herein as PRO1277 polypeptides.

[0109] 45. PRO1135

[0110] Glycosylation is an important mechanism for modulating thephysiochemical and biological properties of proteins in a stage- andtissue-specific manner. One of the important enzymes involved inglycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, anenzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2during the formation of N-linked oligosaccharides. The Saccharomycescerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class Ialpha 1,2-mannosidases that are conserved from yeast to mammals. Giventhe important roles played by the alpha 1,2-mannosidases inglycosylation and the physiochemical activity regulated byglycosylation, there is significant interest in identifying novelpolypeptides having homology to one or more mannosidases. We hereindescribe the identification and characterization of novel polypeptideshaving homology to alpha 1,2-mannosidase protein, designated herein asPRO1135 polypeptides.

[0111] 46. PRO1114

[0112] Interferons (IFNs) encompass a large family of secreted proteinsoccurring in vertebrates. Although they were originally named for theirantiviral activity, growing evidence supports a critical role for IFNsin cell growth and differentiation (Jaramillo et al., CancerInvestigation 13(3):327-338 (1995)). IFNs belong to a class of negativegrowth factors having the ability to inhibit the growth of a widevariety of cells with both normal and transformed phenotypes. IFNtherapy has been shown to be beneficial in the treatment of humanmalignancies such as Karposi's sarcoma, chronic myelogenous leukemia,non-Hodgkin's lymphoma, and hairy cell leukemia as well as in thetreatment of infectious diseases such as hepatitis B (Gamliel et al.,Scanning Microscopy 2(1):485-492 (1988), Einhorn et al., Med. Oncol. &Tumor Pharmacother. 10:25-29 (1993), Ringenberg et al., MissouriMedicine 85(1):21-26 (1988), Saracco et al., Journal of Gastroenterologyand Hepatology 10:668-673 (1995), Gonzalez-Mateos et al.,Hepato-Gastroenteroloy 42:893-899 (1995) and Malaguarnera et al.,Pharmacotherapy 17(5):998-1005 (1997)).

[0113] Interferons can be classified into two major groups based upontheir primary sequence. Type I interferons, IFN-α and IFN-β, are encodedby a superfamily of intronless genes consisting of the IFN-α gene familyand a single IFN-β gene that are thought to have arisen from a commonancestral gene. Type I interferons may be produced by most cell types.Type II IFN, or IFN-γ, is restricted to lymphocytes (T cells and naturalkiller cells) and is stimulated by nonspecific T cell activators orspecific antigens in vivo.

[0114] Although both type I and type II IFNs produce similar antiviraland antiproliferative effects, they act on distinct cell surfacereceptors, wherein the binding is generally species specific (Langer etal., Immunol. Today 9:393400 (1988)). Both IFN-α and IFN-β bindcompetitively to the same high affinity type I receptor, whereas IFN-γbinds to a distinct type II receptor. The presence and number of IFNreceptors on the surface of a cell does not generally reflect thesensitivity of the cell to IFN, although it is clear that the effects ofthe IFN protein is mediated through binding to a cell surface interferonreceptor. As such, the identification and characterization of novelinterferon receptor proteins is of extreme interest.

[0115] We herein describe the identification and characterization ofnovel interferon receptor polypeptides, designated herein as “PRO1114interferon receptor” polypeptides. Thus, the PRO1114 polypeptides of thepresent invention represents a novel cell surface interferon receptor.

[0116] 47. PRO828

[0117] Glutathione peroxidases are of interest because they playimportant roles in protection against risk of coronary disease,atherosclerosis, platelet hyperaggregation and synthesis of proaggregantand proinflammatory compounds. Glutathione peroxidases are involved inthe reduction of hydrogen peroxides and lipid peroxides, which in turnregulate the activities of cyclooxygenase and lipooxygenase pathways.This ultimately influences the production of eicosanoids and modulatesthe balance between a proaggregatory and antiaggregatory state ofplatelets. These and other activities and functions of glutathioneperoxidases are discussed in greater detail by Ursini et al., Biomed.Environ. Sci 10(2-3): 327-332 (1997); Vitoux et al., Ann. Biol. Clin(Paris) 54(5): 181-187 (1996); and Mirault et al., Ann N.Y. Acad. Sci738: 104-115 (1994).

[0118] We herein describe the identification and characterization ofnovel polypeptides having sequence identity with glutathioneperoxidases, designated herein as PRO828 polypeptides.

[0119] 48. PRO1009

[0120] Long chain acyl-CoA synthetase converts free fatty acids toacyl-CoA esters. This synthetase has been reported to have interestingcharacteristics. Specifically, it has been reported that two boys havingAlport syndrome, elliptocytosis and mental retardation carried a largedeletion where long chain acyl-CoA synthetase 4 would have been located.Thus, the absence of this enzyme is believed to play a role in thedevelopment of mental retardation or other signs associated with Alportsyndrome in the family. Piccini, et al., Genomics, 47(3):350-358 (1998).Moreover, it has been reported that an inhibitor of acyl coenzyme Asynthetase, triacsin C, inhibits superoxide anion generation anddegranulation by human neutrophils. Thus, it is suggested that there isa role for acyl-CoA esters in regulating activation of 02 generation anddegranulation at the G protein or subsequent step(s). Korchak, et al.,J. Biol. Chem., 269(48):30281-30287 (1994). Long chain acyl-CoAsynthetase is also briefly discussed in a report which describes verylong chain acyl-CoA synthetase. Uchiyama, et al., J. Biol. Chem.,271(48):30360 (1994). Thus, long chain acyl-CoA synthetase andparticular novel polypeptides having sequence identity therewith are ofinterest.

[0121] We herein describe the identification and characterization ofnovel polypeptides having sequence identity with long chain acyl-CoAsynthetase, designated herein as PRO1009 polypeptides.

[0122] 49. PRO1007

[0123] Glycosylphosphatidylinositol (GPI) anchored proteoglycans aregenerally localized to the cell surface and are thus known to beinvolved in the regulation of responses of cells to numerous growthfactors, cell adhesion molecules and extracellular matrix components.The metastasis-associated GPI-anchored protein (MAGPIAP) is one of thesecell surface proteins which appears to be involved in metastasis.Metastasis is the form of cancer wherein the transformed or malignantcells are traveling and spreading the cancer from one site to another.Therefore, identifying the polypeptides related to metastasis andMAGPIAP is of interest.

[0124] We herein describe the identification and characterization ofnovel polypeptides having sequence identity with MAGPIAP, designatedherein as PRO1007 polypeptides.

[0125] 50. PRO1056

[0126] Mammalian cell membranes perform very important functionsrelating to the structural integrity and activity of various cells andtissues. Of particular interest in membrane physiology is the study oftransmembrane ion channels which act to directly control a variety ofphysiological, pharmacological and cellular processes. Numerous ionchannels have been identified including calcium (Ca), sodium (Na),chloride (Cl) and potassium (K) channels, each of which have beenanalyzed in detail to determine their roles in physiological processesin vertebrate and insect cells. These roles include such things asmaintaining cellular homeostasis, intracellular signaling, and the like.Given the obvious importance of the ion channels, there is significantinterest in identifying and characterizing novel polypeptides havinghomology to one or more ion channels. We herein describe theidentification and characterization of novel polypeptides havinghomology to a chloride channel protein, designated herein as PRO1056polypeptides.

[0127] 51. PRO826

[0128] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO826 polypeptides.

[0129] 52. PRO819

[0130] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO819 polypeptides.

[0131] 53. PRO1006

[0132] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1006 polypeptides.

[0133] 54. PRO1112

[0134] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1112 polypeptides.

[0135] 55. PRO1074

[0136] Many membrane-bound enzymatic proteins play important roles inthe chemical reactions involved in metabolism, including thebiosynthesis of macromolecules, the controlled release and utilizationof chemical energy, development of tissues, and other processesnecessary to sustain life. Galactosyltransferases are a family ofenzymes that play a variety of important metabolic roles and thus arethe subject of interest in research and industry. Numerous referenceshave been published on the identification of galactosyltransferases andthe roles they play in cellular development, maintenance, anddysfunction.

[0137] We herein describe the identification and characterization ofnovel polypeptides having homology to galactosyltransferases, designatedherein as PRO1074 polypeptides.

[0138] 56. PRO1005

[0139] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1005 polypeptides.

[0140] 57. PRO1073

[0141] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1073 polypeptides.

[0142] 58. PRO1152

[0143] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1152 polypeptides.

[0144] 59. PRO1136

[0145] PDZ domain-containing proteins assist formation of cell-celljunctions and localization of membrane protein receptors and ionchannels (Daniels et al., Nat. Struct. Biol. 5:317-325 (1998) and Ullmeret al., FEBS Lett. 424:63-68 (1998)). PDZ domains interact with theC-terminal residues of a particular target membrane protein. Based ontheir binding specificities and sequence homologies, PDZ domains fallinto two classes, class I and class II. In light of the obviousimportance of the PDZ domain-containing proteins, there is significantinterest in identifying novel polypeptides that have homology to thoseproteins. We herein describe the identification and characterization ofnovel polypeptides having homology to PDZ domain-containing proteins,designated herein as PRO1136 polypeptides.

[0146] 60. PRO813

[0147] Surfactant proteins play extremely important biological roles inthe mammalian pulmonary system. One mammalian protein that has beenstudied and well characterized is pulmonary surfactant-associatedprotein C. For example, Qanbar et al., Am. J. Physiol. 271:L572-L580(1996) studied the effect of palmitoylation of pulmonarysurfactant-associated protein C on the surface activity of phospholipidmixtures. Specifically, the authors demonstrated that palmitoylation ofpulmonary surfactant-associated protein C greatly enhanced lipidrespreading and film stability and, therefore, was extremely importantfor surfactant function. Given the obvious important roles played bysurfactant protein in the mammalian organism, there is significantinterest in identifying novel polypeptides having homology to one ormore surfactant enzymes. We herein describe the identification andcharacterization of novel polypeptides having homology to pulmonarysurfactant-associated protein, designated herein as PRO813 polypeptides.

[0148] 61. PRO809

[0149] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO809 polypeptides.

[0150] 62. PRO791

[0151] Of particular interest are novel proteins which have sequenceidentity with known proteins. For example, novel proteins having somesequence identity with the major histocompatibility complex (MHC) are ofinterest. The MHC complex is a region of multiple loci that play majorroles in determining whether transplanted tissue will be accepted asself (histocompatible) or rejected as foreign (histoincompatible).Moreover, the MHC plays a central role in the development of bothhumoral and cell-mediated immune responses. There are class I, II andIII MHC antigens, all known in the art. Class I antigens areglycoproteins expressed on the surface of nearly all nucleated cells,where they present peptide antigens of altered self-cells necessary forthe activation of Tc cells. The assembly of MHC class I antigens isfurther described in Kvist and Levy, Semin. Immunol., 5(2):105-116(1993) and Maffei, et al., Hum. Immunol., 54(2):91-103 (1997).

[0152] We herein describe the identification and characterization ofnovel polypeptides having sequence identity to various MHC-I antigens,designated herein as PRO791 polypeptides.

[0153] 63. PRO1004

[0154] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1004 polypeptides.

[0155] 64. PRO1111

[0156] Protein-protein interactions include receptor and antigencomplexes and signaling mechanisms. As more is known about thestructural and functional mechanisms underlying protein-proteininteractions, protein-protein interactions can be more easilymanipulated to regulate the particular result of the protein-proteininteraction. Thus, the underlying mechanisms of protein-proteininteractions are of interest to the scientific and medical community.

[0157] All proteins containing leucine-rich repeats are thought to beinvolved in protein-protein interactions. Leucine-rich repeats are shortsequence motifs present in a number of proteins with diverse functionsand cellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415-421 (October 1994).

[0158] A study has been reported on leucine-rich proteoglycans whichserve as tissue organizers, orienting and ordering collagen fibrilsduring ontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141-174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215-222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bernard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO91/0727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factorβ hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

[0159] Another protein which has been reported to have leucine-richrepeats is the SLIT protein which has been reported to be useful intreating neuro-degenerative diseases such as Alzheimer's disease, nervedamage such as in Parkinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO92/0518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland),125(1-2):65-70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.,6(4):1125-1133 (October 1995) (kidney disease involvement).

[0160] We herein describe the identification and characterization ofnovel polypeptides having homology to LIG, designated herein as PRO1111polypeptides.

[0161] 65. PRO1344

[0162] Factor C is a protein that is intimately involved with thecoagulation cascade in a variety of organisms. The coagulation cascadehas been shown to involve numerous different intermediate proteins,including factor C, all of whose activity is essential to the properfunctioning of this cascade. Abnormal coagulation cascade function canresult in a variety of serious abnormalities and, as such, theactivities of the coagulation cascade proteins is of particularinterest. As such, efforts are currently being undertaken to identifynovel polypeptides having homology to one or more of the coagulationcascade proteins.

[0163] We herein describe the identification and characterization ofnovel polypeptides having homology to factor C protein, designatedherein as PRO1344 polypeptides.

[0164] 66. PRO1109

[0165] Carbohydrate chains on glycoproteins are important not only forprotein conformation, transport and stability, but also for cell-celland cell-matrix interactions. β-1,4-galactosyltransferase is an enzymethat is involved in producing carbohydrate chains on proteins, whereinthe β-1,4-galactosyltransferase enzyme acts to transfer galactose to theterminal N-acetylglucosamine of complex-type N-glycans in the Golgiapparatus (Asano et al., EMBO J. 16:1850-1857 (1997)). In addition, ithas been suggested that β-1,4-galactosyltransferase is invloved directlyin cell-cell interactions during fertilization and early embryogenesisthrough a subpopulation of this enzyme distributed on the cell surface.Specifically, Lu et al., Development 124:41214131 (1997) and Larson etal., Biol. Reprod. 57:442453 (1997) have demonstrated thatβ-1,4-galactosyltransferase is expressed on the surface of sperm from avariety of mammalian species, thereby suggesting an important role infertilization. In light of the above, novel polypeptides having sequenceidentity to β-1,4-galactosyltransferase are of interest.

[0166] We herein describe the identification and characterization ofnovel polypeptides having homology to β-1,4-galactosyltransferase,designated herein as PRO1109 polypeptides.

[0167] 67. PRO1383

[0168] The nmb gene is a novel gene that encodes a putativetransmembrane glycoprotein which is differentially expressed inmetastatic human melanoma cell lines and which shows substantialhomology to the precursor of pMEL17, a melanocyte-specific protein(Weterman et al., Int. J. Cancer 60:73-81 (1995)). Given the interest inidentifying tumor-specific cell-surface polypeptide markers, there issubstantial interest in novel polypeptides having homology to nmb. Weherein describe the identification and characterization of novelpolypeptides having homology to the nmb protein, designated herein asPRO1383 polypeptides.

[0169] 68. PRO1003

[0170] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1003 polypeptides.

[0171] 69. PRO1108

[0172] Lysophosphatidic acid acyltransferase (LPAAT) is an enzyme thatin lipid metabolism converts lysophosphatidic acid (LPA) intophosphatidic acid (PA). LPA is a phospholipid that acts as anintermediate in membrane phospholipid metabolism. Various LPAAT enzymeshave been identified in a variety of species (see, e.g., Aguado et al.,J. Biol. Chem. 273:4096-4105 (1998), Stamps et al., Biochem. J.326:455-461 (1997), Eberhart et al., J. Biol. Chem. 272:20299-20305(1997) and West et al., DNA Cell Biol. 16:691-701 (1997)). Given theobvious importance of LPAAT in a variety of different applicationsincluding cell membrane maintenance, there is substantial interest inidentifying and characterizing novel polypeptides having homology toLPAAT. We herein describe the identification and characterization ofnovel polypeptides having homology to LPAAT protein, designated hereinas PRO1108 polypeptides.

[0173] 70. PRO1137

[0174] A particular class of secreted polypeptides that are of interestin research and industry are ribosyltransferases. Braren et al.described the use of EST databases for the identification and cloning ofnovel ribosyltransferase gene family members (Adv. Exp. Med. Biol.419:163-168 (1997)). Ribosyltransferases have been identified playingroles in a variety of metabolic functions including posttranslationalmodification of proteins (Saxty et al., J. Leukoc. Biol., 63(1):15-21(1998)), and mediation of the assembly of filamentous actin andchemotaxis in polymorphonuclear neutrophil leukocytes (Kefalas et al.Adv. Exp. Med. Biol. 419:241-244 (1997)).

[0175] Described herein is the identification and characterization ofnovel polypeptides having homology to ribosyltransferase, designatedherein as PRO1137 polypeptides.

[0176] 71. PRO1138

[0177] Efforts are being undertaken by both industry and academia toidentify new, native receptor proteins. Many efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel receptor proteins. Of particular interest is theidentification of membrane-bound proteins found in cells of thehematopoietic system, as they often play important roles in fightinginfection, repair of injured tissues, and other activities of cells ofthe hematopoietic system. For instance, CD84 leukocyte antigen hasrecently been identified as a new member of the Ig superfamily (de laFuente et al., Blood, 90(6):2398-2405 (1997)).

[0178] Described herein is the identification and characterization of anovel polypeptide having homology to CD84 leukocyte antigen, designatedherein as PRO1138 polypeptides.

[0179] 72. PRO1054

[0180] The proteins of the major urinary protein complex (MUP), proteinswhich are members of the lipocalin family, function to bind to volatilepheromones and interact with the vomeronasal neuroepithelium of theolfactory system. As such, proteins in the MUP family are intimatelyinvolved in the process of attraction between mammals of differentsexes. Many different MUP family members have been identified andcharacterized and shown to possess varying degrees of amino acidsequence homology (see, e.g., Mucignat et al., Chem. Senses 23:67-70(1998), Ferrari et al., FEBS Lett. 401:73-77 (1997) and Bishop et al.,EMBO J. 1:615-620 (1982)). Given the physiological and biologicalimportance of the MUP family of proteins, there is significant interestin identifying and characterizing novel members of this family. Weherein describe the identification and characterization of novelpolypeptides having homology to MUP family of proteins, designatedherein as PRO1054 polypeptides.

[0181] 73. PRO994

[0182] The L6 cell surface antigen, which is highly expressed on lung,breast, colon, and ovarian carcinomas, has attracted attention as apotential therapeutic target for murine monoclonal antibodies and theirhumanized counterparts (Marken et al., Proc. Natl. Acad. Sci. USA89:3503-3507 (1992)). The cDNA encoding this tumor-associated cellsurface antigen has been expressed in COS cells and shown to encode a202 amino acid polypeptide having three transmembrane domains. The L6antigen has been shown to be related to a number of cell surfaceproteins that have been implicated in the regulation of cell growth,including for example CD63 and CO-029, proteins which are also highlyexpressed on tumor cells. As such, there is significant interest inidentifying novel polypeptides having homology to the L6 tumor cellantigen as potential targets for cancer therapy. We herein describe theidentification and characterization of novel polypeptides havinghomology to the L6 cell surface tumor cell-associated antigen,designated herein as PRO994 polypeptides.

[0183] 74. PRO812

[0184] Steroid binding proteins play important roles in numerousphysiological processes associated with steroid function. Specifically,one steroid binding protein-associated polypeptide that has been wellcharacterized is component 1 of the prostatic binding protein. Component1 of the prostatic binding protein has been shown to be specific forsubunit F of the prostatic binding protein, the major secretoryglycoprotein of the rat ventral prostate (Peeters et al., Eur. J.Biochem. 123:55-62 (1982) and Liao et al., J. Biol. Chem. 257:122-125(1982)). The amino acid sequence of component 1 of the prostatic bindingprotein has been determined, wherein the sequence is highly rich inglutamic acid residues and is overall highly acidic. This protein playsan important role in the response of the prostate gland to steroidhormones. We herein describe the identification and characterization ofnovel polypeptides having homology to prostatic steroid-binding proteinc1, designated herein as PRO812 polypeptides.

[0185] 75. PRO1069

[0186] Of particular interest is the identification of newmembrane-bound proteins involved in ion conductance such as channelinhibitory factor (CHIF) and MAT-8, which have recently been reported(see Wald et al., Am. J. Physiol, 272(5 pt 2): F617-F623 (1997); Capurroet al., Am. J. Physiol, 271(3 pt 1): C753-C762 (1996); Wald et al., Am.J. Physiol, 271(2 pt 2): F322-F329 (1996); and Morrison et al., J. Biol.Chem 270(5):2176-2182 (1995)).

[0187] Described herein is the identification and characterization ofnovel polypeptides having homology to CHIF and MAT-8 polypeptides,designated herein as PRO1069 polypeptides.

[0188] 76. PRO1129

[0189] Cytochromes P-450 are a superfamily of hemoproteins whichrepresent the main pathway for drug and chemical oxidation (Horsmans,Acta Gastroenterol. Belg. 60:2-10 (1997)). This superfamily is dividedinto families, subfamilies and/or single enzymes. Recent reports haveprovided a great deal of information concerning the cytochrome P-450isozymes and increased awareness of life threatening interactions withsuch commonly prescribed drugs as cisapride and some antihistamines(Michalets, Pharmacotherapy 18:84-112 (1998) and Singer et al., J. Am.Acad. Dermatol. 37:765-771 (1997)). Given this information, there issignificant interest in identifying novel members of the cytochromeP-450 family of proteins. We herein describe the identification andcharacterization of novel polypeptides having homology to cytochromeP-450 proteins, designated herein as PRO1129 polypeptides.

[0190] 77. PRO1068

[0191] Urotensins are neurosecretory proteins that are of interestbecause of their potential roles in a variety of physiological processesincluding smooth muscle contraction (Yano et al. Gen. Comp. Endocrinol.96(3): 412-413 (1994)), regulation of arterial blood pressure and heartrate (Le Mevel et al. Am. J. Physiol. 271(5 Pt 2): R1335-R1343 (1996)),and corticosteroid secretion (Feuilloley et al. J. Steroid Biochem Mol.Biol. 48(2-3): 287-292 (1994)).

[0192] We herein describe the identification and characterization ofnovel polypeptides having homology to urotensin, designated herein asPRO1068 polypeptides.

[0193] 78. PRO1066

[0194] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1066 polypeptides.

[0195] 79. PRO1184

[0196] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1184 polypeptides.

[0197] 80. PRO1360

[0198] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1360 polypeptides.

[0199] 81. PRO1029

[0200] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1029 polypeptides.

[0201] 82. PRO1139

[0202] Obesity is the most common nutritional disorder which, accordingto recent epidemiologic studies, affects about one third of allAmericans 20 years of age or older. Kuczmarski et al., J. Am. Med.Assoc. 272, 205-11 (1994). Obesity is responsible for a variety ofserious health problems, including cardiovascular disorders, type IIdiabetes, insulin-resistance, hypertension, hypertriglyceridemia,dyslipoproteinemia, and some forms of cancer. Pi-Sunyer, F. X., Anns.Int. Med. 119, 655-60 (1993); Colfitz, G. A., Am. J. Clin. Nutr. 55,503S-507S (1992). A single-gene mutation (the obesity or “ob” mutation)has been shown to result in obesity and type II diabetes in mice.Friedman, Genomics 11, 1054-1062 (1991). Zhang et al., Nature 372,425-431 (1994) have recently reported the cloning and sequencing of themouse ob gene and its human homologue, and suggested that the ob geneproduct may function as part of a signaling pathway from adipose tissuethat acts to regulate the size of the body fat depot. Parabiosisexperiments performed more than 20 years ago predicted that thegenetically obese mouse containing two mutant copies of the ob gene(ob/ob mouse) does not produce a satiety factor which regulates its foodintake, while the diabetic (db/db) mouse produces but does not respondto a satiety factor. Coleman and Hummal, Am. J. Physiol. 217, 1298-1304(1969); Coleman, Diabetol. 9, 294-98 (1973). OB proteins are disclosed,for example, in U.S. Pat. Nos. 5,532,336; 5,552,522; 5,552,523;5,552,514; 5,554,727. Recent reports by three independent research teamshave demonstrated that daily injections of recombinant OB proteininhibit food intake and reduce body weight and fat in grossly obeseob/ob mice but not in db/db mice (Pelleymounter et al., Science 269,540-43 [1995]; Halaas et al., Science 269, 543-46 [1995]; Campfield etal., Science 269, 546-49 [1995]), suggesting that the ob protein is sucha satiety factor as proposed in early cross-circulation studies.

[0203] A receptor of the OB protein (OB-R) is disclosed in Tartaglia etal., Cell 83, 1263-71 (1995). The OB-R is a single membrane-spanningreceptor homologous to members of the class I cytokine receptor family(Tartaglia et al., supra; Bazan, Proc. Natl. Acad. Sci. USA 87,6934-6938 [1990]). Two 5′-untranslated regions and several3′-alternative splice variants encoding OB-R with cytoplasmic domains ofdifferent lengths have been described in mouse, rat and human (Chen etal., Cell 84, 491-495 [1996]; Chua et al., Science 271, 994-996 [1996];Tartaglia et al., supra; Wang et al., FEBS Lett. 392:87-90 [1996];Phillips et al., Nature Genet. 13, 18-19 [1996]; Cioffi et al., NatureMed., 2 585-589 [1996]). A human hematopoetin receptor, which might be areceptor of the CB protein, is described in PCT application PublicationNo. WO 96/08510, published Mar. 21, 1996.

[0204] Bailleul et al., Nucl. Acids Res. 25, 2752-2758 (1997) identifieda human mRNA splice variant of the OB-R gene that potentially encodes anovel protein, designated as leptin receptor gene-related protein(OB-RGRP). This protein displays no sequence similarity to the leptinreceptor itself. The authors found that the OB-RGRP gene shares itspromoter and two exons with the OB-R gene, and suggested that there is arequirement for a coordinate expression of OB-R and OB-RGRP to elicitthe full physiological response to leptin in vivo.

[0205] 83. PRO1309

[0206] Protein-protein interactions include receptor and antigencomplexes and signaling mechanisms. As more is known about thestructural and functional mechanisms underlying protein-proteininteractions, protein-protein interactions can be more easilymanipulated to regulate the particular result of the protein-proteininteraction. Thus, the underlying mechanisms of protein-proteininteractions are of interest to the scientific and medical community.

[0207] All proteins containing leucine-rich repeats are thought to beinvolved in protein-protein interactions. Leucine-rich repeats are shortsequence motifs present in a number of proteins with diverse functionsand cellular locations. The crystal structure of ribonuclease inhibitorprotein has revealed that leucine-rich repeats correspond to beta-alphastructural units. These units are arranged so that they form a parallelbeta-sheet with one surface exposed to solvent, so that the proteinacquires an unusual, nonglubular shape. These two features have beenindicated as responsible for the protein-binding functions of proteinscontaining leucine-rich repeats. See, Kobe and Deisenhofer, TrendsBiochem. Sci., 19(10):415-421 (October 1994); Kobe and Deisenhofer,Curr. Opin. Struct. Biol., 5(3):409-416 (1995).

[0208] A study has been reported on leucine-rich proteoglycans whichserve as tissue organizers, orienting and ordering collagen fibrilsduring ontogeny and are involved in pathological processes such as woundhealing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit.Rev. Biochem. Mol. Biol., 32(2):141-174 (1997). Others studiesimplicating leucine rich proteins in wound healing and tissue repair areDe La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany),37(4):215-222 (1995), reporting mutations in the leucine rich motif in acomplex associated with the bleeding disorder Bernard-Soulier syndrome,Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-116 (July1995), reporting that platelets have leucine rich repeats and Ruoslahti,E. I., et al., WO91/0727-A by La Jolla Cancer Research Foundationreporting that decorin binding to transforming growth factors hasinvolvement in a treatment for cancer, wound healing and scarring.Related by function to this group of proteins is the insulin like growthfactor (IGF), in that it is useful in wound-healing and associatedtherapies concerned with re-growth of tissue, such as connective tissue,skin and bone; in promoting body growth in humans and animals; and instimulating other growth-related processes. The acid labile subunit ofIGF (ALS) is also of interest in that it increases the half-life of IGFand is part of the IGF complex in vivo.

[0209] Another protein which has been reported to have leucine-richrepeats is the SLIT protein which has been reported to be useful intreating neuro-degenerative diseases such as Alzheimer's disease, nervedamage such as in Parkinson's disease, and for diagnosis of cancer, see,Artavanistsakonas, S. and Rothberg, J. M., WO92/0518-A1 by YaleUniversity. Of particular interest is LIG-1, a membrane glycoproteinthat is expressed specifically in glial cells in the mouse brain, andhas leucine rich repeats and immunoglobulin-like domains. Suzuki, etal., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studiesreporting on the biological functions of proteins having leucine richrepeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland),125(1-2):65-70 (December 1996) (gonadotropin receptor involvement);Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996)(apoptosis involvement); Harris, P. C., et al., J. Am. Soc. Nephrol.,6(4): 1125-1133 (October 1995) (kidney disease involvement).

[0210] Efforts are therefore being undertaken by both industry andacademia to identify new proteins having leucine rich repeats to betterunderstand protein-protein interactions. Of particular interest arethose proteins having leucine rich repeats and homology to knownproteins having leucine rich repeats such as platelet glycoprotein V,SLIT and ALS. Many efforts are focused on the screening of mammalianrecombinant DNA libraries to identify the coding sequences for novelmembrane-bound proteins having leucine rich repeats.

[0211] 84. PRO1028

[0212] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1028 polypeptides.

[0213] 85. PRO1027

[0214] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1027 polypeptides.

[0215] 86. PRO1107

[0216] Of particular interest are novel proteins having some sequenceidentity to known proteins. Known proteins include PC-1, an ecto-enzymepossessing alkaline phosphodiesterase I and nucleotide pyrophosphataseactivities, further described in Belli et al., Eur. J. Biochem.,228(3):669-676 (1995). Phosphodiesterases are also described in Fuss etal., J. Neurosci., 17(23):9095-9103 (1997) and Scott et al., Hematology,25(4):995-1002 (1997). Phosphodiesterase I, is described as a noveladhesin molecule and/or cytokine (related to autotaxin) involved inoligodendrocyte function. Fuss, supra.

[0217] We herein describe the identification and characterization ofnovel polypeptides having homology nto PC-1, designated herein asPRO1107 polypeptides.

[0218] 87. PRO1140

[0219] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1140 polypeptides.

[0220] 88. PRO1106

[0221] As the mitochondria is primarily responsible for generatingenergy, proteins associated with the mitochondria are of interest.Recently, a cDNA from a novel Ca⁺⁺-dependent member of the mitochondrialsolute carrier superfamily was isolated from a rabbit small intestinalcDNA library as described in Weber, et al., PNAS USA, 94(16):8509-8514(1997). It was reported that this transporter has four elongationfactor-hand motifs in the N-terminal and is localized in the peroxisome,although a fraction can be found in the mitochondria. Thus, thistransporter, and proteins which have sequence identity to this and othermembers of the mitochondrial solute carrier superfamily are ofparticular interest.

[0222] We herein describe the identification and characterization ofnovel polypeptides having homology to a peroxisomal calcium dependentsolute carrier protein, designated herein as PRO1106 polypeptides.

[0223] 89. PRO1291

[0224] Butyrophilin is a milk glycoprotein that constitutes more than40% of the total protein associated with the fat globule membrane inmammalian milk. Expression of butyrophilin mRNA has been shown tocorrelate with the onset of milk fat production toward the end pregnancyand is maintained throughout lactation. Butyrophilin has been identifiedin bovine, murine and human (see Taylor et al., Biochim. Biophys. Acta1306:1-4 (1996), Ishii et al., Biochim. Biophys. Acta 1245:285-292(1995), Mather et al., J. Dairy Sci. 76:3832-3850 (1993) and Banghart etal., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembraneprotein that is incorporated into the fat globulin membrane. It has beensuggested that butyrophilin may play a role as the principle scaffoldfor the assembly of a complex with xanthine dehydrogenase/oxidase andother proteins that function in the budding and release of milk-fatglobules from the apical surface during lactation (Banghart et al.,supra).

[0225] Given that butyrophilin plays an obviously important role inmammalian milk production, there is substantial interest in identifyingnovel butyrophilin homologs. We herein describe the identification andcharacterization of novel polypeptides having homology to butyrophilin,designated herein as PRO1291 polypeptides.

[0226] 90. PRO1105

[0227] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1105 polypeptides.

[0228] 91. PRO511

[0229] Proteins of interest include those having sequence identity withRoBo-1, a novel member of the urokinase plasminogen activatorreceptor/CD59/Ly-6/snake toxin family selectively expressed in bone andgrowth plate cartilage as described in Noel et al., J. Biol. Chem.273(7):3878-3883 (1998). RoBo-1 is believed to play a novel role in thegrowth or remodeling of bone. Proteins also of interest include thosehaving sequence identity with phospholipase inhibitors.

[0230] We herein describe the identification and characterization ofnovel polypeptides having homology to urokinase plasminogen activatorreceptors and phospholipase inhibitors, designated herein as PRO511polypeptides.

[0231] 92. PRO1104

[0232] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1104 polypeptides.

[0233] 93. PRO1100

[0234] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1100 polypeptides.

[0235] 94. PRO836

[0236] Of interest are luminal proteins, or proteins specific to theendoplasmic reticulum (ER). Of particular interest are proteins havingsequence identity with known proteins. Known proteins include proteinssuch as SLS1. In Saccharomyces cerevisiae, SLS1 has been reported to bea mitochondrial integral membrane protein involved in mitochondrialmetabolism. Rouillard, et al., Mol. Gen. Genet., 252(6):700-708 (1996).In yeast Yarrowia lipolytica, it has been reported that the SLS1 geneproduct (SLS1p) behaves as a lumenal protein of the ER. It is believedthat SPS1p acts in the preprotein translocation process, interactingdirectly with translocating polypeptides to facilitate their transferand/or help their folding in the ER. Bosirame, et al., J. Biol. Chem.,271(20):11668-11675 (1996).

[0237] We herein describe the identification and characterization ofnovel polypeptides having homology to SLS1, designated herein as PRO836polypeptides.

[0238] 95. PRO1141

[0239] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1141 polypeptides.

[0240] 96. PRO1132

[0241] Proteases are enzymatic proteins which are involved in a largenumber of very important biological processes in mammalian andnon-mammalian organisms. Numerous different protease enzymes from avariety of different mammalian and non-mammalian organisms have beenboth identified and characterized, including the serine proteases whichexhibit specific activity toward various serine-containing proteins. Themammalian protease enzymes play important roles in biological processessuch as, for example, protein digestion, activation, inactivation, ormodulation of peptide hormone activity, and alteration of the physicalproperties of proteins and enzymes.

[0242] Neuropsin is a novel serine protease whose mRNA is expressed inthe central nervous system. Mouse neuropsin has been cloned, and studieshave shown that it is involved in the hippocampal plasticity. Neuropsinhas also been indicated as associated with extracellular matrixmodifications and cell migrations. See, generally, Chen, et al.,Neurosci., 7(2):5088-5097 (1995) and Chen, et al., J. Histochem.Cytochem., 46:313-320 (1998).

[0243] Another serine protease of interest is the enamel matrix serineproteinase. The maturation of dental enamel succeeds the degradation oforganic matrix. Inhibition studies have shown that this degradation isaccomplished by a serine-type proteinase. Proteases associated withenamel maturation are described in, i.e., Simmer, et al., J. Dent. Res.,77(2):377-386 (1998), Overall and Limeback, Biochem J., 256(3):965-972(1988), and Moradian-Oldak, Connect. Tissue Res., 35(14):231-238 (1996).

[0244] We herein describe the identification and characterization ofnovel polypeptides having homology to serine proteases, designatedherein as PRO1132 polypeptides.

[0245] 97. PRO1346

[0246] The abbreviations “TIE” or “tie” are acronyms, which stand for“tyrosine kinase containing Ig and EGF homology domains” and were coinedto designate a new family of receptor tyrosine kinases which are almostexclusively expressed in vascular endothelial cells and earlyhemopoietic cells, and are characterized by the presence of an EGF-likedomain, and extracellular folding units stabilized by intra-chaindisulfide bonds, generally referred to as “immunoglobulin (IG)-like”folds. A tyrosine kinase homologous cDNA fragment from human leukemiacells (tie) was described by Partanen et al., Proc. Natl. Acad. Sci. USA87, 8913-8917 (1990). The mRNA of this human “TIE” receptor has beendetected in all human fetal and mouse embryonic tissues, and has beenreported to be localized in the cardiac and vascular endothelial cells.Korhonen et al., Blood 80, 2548-2555 (1992); PCT Application PublicationNo. WO 93/14124 (published Jul. 22, 1993). The rat homolog of human TIE,referred to as “TIE-1”, was identified by Maisonpierre et al., Oncogene8, 1631-1637 (1993)). Another TIE receptor, designated “TIE-2” wasoriginally identified in rats (Dumont et al., Oncogene 8, 1293-1301(1993)), while the human homolog of TIE2, referred to as “ork” wasdescribed in U.S. Pat. No. 5,447,860 (Ziegler). The murine homolog ofTIE-2 was originally termed “tek.” The cloning of a mouse TIE-2 receptorfrom a brain capillary cDNA library is disclosed in PCT ApplicationPublication No. WO 95/13387 (published May 18, 1995). TIE-2 is areceptor tyrosine kinase that is expressed almost exclusively byvascular endothelium. Tie-2 knockout mice die by defects in theformation of microvassels. Accordingly, the TIE receptors are believedto be actively involved in angiogenesis, and may play a role inhemopoiesis as well. Indeed, recent results (Lin et al., J. Clin.Invest. 100(8), 2072-2078 [1997]) demonstrating the ability of a solubleTIE-2 receptor to inhibit tumor angiogenesis have been interpreted toindicate that TIE-2 plays a role in pathologic vascular growth. Inanother study, TIE-2 expression was examined in adult tissues undergoingangiogenesis and in quiescent tissues. TIE2 expression was localized byimmunohistochemistry to the endothelium of neovessels in rat tissuesundergoing angiogenesis during hormonally stimulated follicularmaturation and uterine development and in healing wounds. TIE-2 was alsoreported to be expressed in the entire spectrum of the quiescentvasculature (arteries, veins, and capillaries) in a wide range of adulttissues. Wong et al., Circ. Res. 81(4), 567-574 (1997). It has beensuggested that TIE-2 has a dual function in adult angiogenesis andvascular maintenance.

[0247] The expression cloning of human TIE-2 ligands has been describedin PCT Application Publication No. WO 96/11269 (published Apr. 18, 1996)and in U.S. Pat. No. 5,521,073 (published May 28, 1996). A vectordesignated as λgt10 encoding a TIE-2 ligand NL7d “htie-2 ligand 1” or“hTL1” has been deposited under ATCC Accession No. 75928. A plasmidencoding another TIE-2 ligand designated “htie-2 2” or “hTL2” isavailable under ATCC Accession No. 75928. This second ligand has beendescribed as an antagonist of the TAI-2 receptor. The identification ofsecreted human and mouse ligands for the TIE-2 receptor has beenreported by Davis et al., Cell 87, 1161-1169 (1996). The human liganddesignated “Angiopoietin-1”, to reflect its role in angiogenesis andpotential action during hemopoiesis, is the same ligand as the ligandvariously designated as “htie-2 1” or “hTL-1” in WO 96/11269.Angiopoietin-1 has been described to play an angiogenic role later anddistinct from that of VEGF (Suri et al., Cell 87, 1171-1180 (1996)).Since TIE-2 is apparently upregulated during the pathologic angiogenesisrequisite for tumor growth (Kaipainen et al., Cancer Res. 54, 6571-6577(1994)) angiopoietin-1 has been suggested to be additionally useful forspecifically targeting tumor vasculature (Davis et al., supra).

[0248] We herein describe the identification and characterization ofnovel TIE ligand polypeptides, designated herein as PRO1346polypeptides.

[0249] 98. PRO1131

[0250] The low density lipoprotein (LDL) receptor is a membrane-boundprotein that plays a key role in cholesterol homeostasis, mediatingcellular uptake of lipoprotein particles by high affinity binding to itsligands, apolipoprotein (apo) B-100 and apoE. The ligand-binding domainof the LDL receptor contains 7 cysteine-rich repeats of approximately 40amino acids, wherein each repeat contains 6 cysteines, which form 3intra-repeat disulfide bonds. These unique structural features providethe LDL receptor with its ability to specifically interact with apoB-100 and apoE, thereby allowing for transport of these lipoproteinparticles across cellular membranes and metabolism of their components.Soluble fragments containing the extracellular domain of the LDLreceptor have been shown to retain the ability to interact with itsspecific lipoprotein ligands (Simmons et al., J. Biol. Chem.272:25531-25536 (1997)). LDL receptors are further described in Javitt,FASEB J., 9(13): 1378-1381 (1995), van Berkel, et al., Atherosclerosis,118 Suppl:S43-S50 (1995) and Herz and Willnow, Ann. NY Acad. Sci.,737:14-19 (1994). Thus, proteins having sequence identity with LDLreceptors are of interest.

[0251] We herein describe the identification and characterization ofnovel polypeptides having homology to LDL receptors, designated hereinas PRO1131 polypeptides.

[0252] 99. PRO1281

[0253] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1281 polypeptides.

[0254] 100. PRO1064

[0255] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel membrane-bound proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1064 polypeptides.

[0256] 101. PRO1379

[0257] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening-of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1379 polypeptides.

[0258] 102. PRO844

[0259] Proteases are enzymatic proteins which are involved in a largenumber of very important biological processes in mammalian andnon-mammalian organisms. Numerous different protease enzymes from avariety of different mammalian and non-mammalian organisms have beenboth identified and characterized. The mammalian protease enzymes playimportant roles in many different biological processes including, forexample, protein digestion, activation, inactivation, or modulation ofpeptide hormone activity, and alteration of the physical properties ofproteins and enzymes. Thus, proteases are of interest. Also of interestare protease inhibitors.

[0260] Of particular interest are serine proteases. In one study it wasreported that when the serine protease inhibitor antileukoproteinase(aLP) is injected, it accumulates in articular and extraarticularcartilage of normal rats. This physiological pathway of cartilageaccumulation, lost in proteoglycan depleted arthritic cartilage isbelieved to serve to maintain the local balance between proteinasefunction and inhibition. Burkhardt, et al., J. Rheumatol, 24(6):1145-1154 (1997). Moreover, aLP and other protease inhibitors have beenreported to play a role in the in vitro growth of hematopoietc cells bythe neutralization of proteinases produced by bone marrow accessorycells. Gosklink, et al., J. Exp. Med., 184(4):1305-1312 (1996). Also ofinterest are mutants of aLP. Oxidation resistant mutants of aLPe havebeen reported to have significant therapeutic effects on animal modelshaving emphysema. Steffens, et al., Agents Actions Suppl., 42:111-121(1993). Thus, serine protease inhibitors are of interest.

[0261] We herein describe the identification and characterization ofnovel polypeptides having homology to serine protease inhibitors,designated herein as PRO844 polypeptides.

[0262] 103. PRO848

[0263] Membrane-bound proteins of interest include channels such as ionchannels. Furthermore, membrane-bound proteins of interest includeenzymes bound to intracellular vacuoles or organelles, such astransferases. For example, a peptide of interest is the GalNAc alpha2,6-sailytransferase as described in Kurosawa, et al., J. Biol. Chem.,269(2):1402-1409 (1994). This peptide was constructed to be secreted,and retained its catalytic activity. The expressed enzyme exhibitedactivity toward asialomucin and asialofetuin, but not otherglycoproteins tested. As sialylation is an important function,sialyltransferases such as this one, and peptides related by sequenceidentity, are of interest.

[0264] We herein describe the identification and characterization ofnovel polypeptides having homology to sialyltransferases, designatedherein as PRO848 polypeptides.

[0265] 104. PRO1097

[0266] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1097 polypeptides.

[0267] 105. PRO1153

[0268] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel transmembrane proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1153 polypeptides.

[0269] 106. PRO1154

[0270] Aminopeptidase N causes enzymatic degradation of perorallyadministered peptide drugs. Thus, aminopeptidase N has been used instudies to develop and identify inhibitors so as to increase theefficacy of peptide drugs by inhibiting their degradation.Aminopeptidases are also generally of interest to use to degradepeptides. Aminopeptidases, particularly novel aminopeptidases aretherefore of interest. Aminopeptidase N and inhibitors thereof arefurther described in Bernkop-Schnurch and Marschutz, Pharm. Res., 14(2):181-185 ((1997); Lerche, et al., Mamm. Genome, 7(9):712-713 (1996);Papapetropoulos, et al., Immunopharmacology, 32(1-3):153-156 (1996);Miyachi, et al., J. Med. Chem., 41(3):263-265 (1998); and Olsen, et al.,Adv. Exp. Med. Biol., 421:47-57 (1997).

[0271] We herein describe the identification and characterization ofnovel polypeptides having homology to aminopeptidase N, designatedherein as PRO1154 polypeptides.

[0272] 107. PRO1181

[0273] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1181 polypeptides.

[0274] 108. PRO1182

[0275] Conglutinin is a bovine serum protein that was originallydescribed as a vertebrate lectin protein and which belongs to the familyof C-type lectins that have four characteristic domains, (1) anN-terminal cysteine-rich domain, (2) a collagen-like domain, (3) a neckdomain and (4) a carbohydrate recognition domain (CRD). Recent reportshave demonstrated that bovine conglutinin can inhibit hemagglutinationby influenza A viruses as a result of their lectin properties (Eda etal., Biochem. J. 316:43-48 (1996)). It has also been suggested thatlectins such as conglutinin can function as immunoglobulin-independentdefense molecules due to complement-mediated mechanisms. Thus,conglutinin has been shown to be useful for purifying immune complexesin vitro and for removing circulating immune complexes from patientsplasma in vivo (Lim et al., Biochem. Biophys. Res. Commun. 218:260-266(1996)). We herein describe the identification and characterization ofnovel polypeptides having homology to conglutinin protein, designatedherein as PRO1182 polypeptides.

[0276] 109. PRO1155

[0277] Substance P and the related proteins, neurokinin A and neurokininB have been reported as compounds which elicit contraction of the ileumboth directly through action on a muscle cell receptor and indirectlythrough stimulation of a neuronal receptor. This action leads to therelease of acetylcholine which causes muscle contraction via muscarinicreceptors. It has also been reported that neurolinin B was found to bethe most potent agonist for the neuronal Substance P receptor and thatneurokinin B can be inhibited by enkephalinamide. Laufer, et al., PNASUSA, 82(21):74444-7448 (1985). Moreover, neurokinin B has been reportedto provide neuroprotection and cognitive enhancement, and thereforebelieved to be useful for the treatment of neurodegenerative disorders,including alzheimers disease. Wenk, et al., Behav. Brain Res.,83(1-2):129-133 (1997). Tachykinins are also described in Chawla, etal., J. Comp. Neurol., 384(3):429-442 (1997). Thus, tachykinins,particularly those related to neurokinin B are of interest.

[0278] We herein describe the identification and characterization ofnovel polypeptides having homology to neurokinin B protein, designatedherein as PRO1155 polypeptides.

[0279] 110. PRO1156

[0280] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1181 polypeptides.

[0281] 111. PRO1098

[0282] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1098 polypeptides.

[0283] 112. PRO1127

[0284] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1127 polypeptides.

[0285] 113. PRO1126

[0286] The extracellular mucous matrix of olfactory neuroepithelium is ahighly organized structure in intimate contact with chemosensory ciliathat house the olfactory transduction machinery. The major proteincomponent of this extracellular matrix is olfactomedin, a glycoproteinthat is expressed in olfactory neuroepithelium and which formintermolecular disulfide bonds so as to produce a polymer (Yokoe et al.,Proc. Natl. Acad. Sci. USA 90:4655-4659 (1993), Bal et al., Biochemistry32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153(1991)). It has been suggested that olfactomedin may influence themaintenance, growth or differentiation of chemosensory cilia on theapical dendrites of olfactory neurons. Given this important role, thereis significant interest in identifying and characterizing novelpolypeptides having homology to olfactomedin. We herein describe theidentification and characterization of novel polypeptides havinghomology to olfactomedin protein, designated herein as PRO1126polypeptides.

[0287] 114. PRO1125

[0288] Of particular interest are proteins which have multiple Trp-Asp(WD) repeats. WD proteins are made up of highly conserved repeatingunits usually ending with WD. They are found in eukaryotes but not inprokaryotes. They regulate cellular functions, such as cell division,cell-fate determination, gene transcription, gene transcription,transmembrane signaling, mRNA modification and vesicle fusion. WD arefurther described in Neer, et al., Nature, 371(6495):297-300 (1994);Jiang and Struhl, Nature, 391(6666):493-496(1998); and DeSilva, et al.,Genetics, 148(2):657-667 (1998). Thus, new members of this superfamilyare all of interest.

[0289] 115. PRO1186

[0290] Protein A from Dendroaspis polylepis polylepis (black mamba)venom comprises 81 amino acids, including ten half-cystine residues.Venoms are of interest on the one hand as weapons in war, and on theother hand, to use in assays to determine agents which reverse orinhibit the effects of the venom or a similar poison. Black mamba venomis further described in Int. J. Biochem., 17(6):695-699 (1985) andJoubert and Strydom, Hoppe Seylers Z Physiol. Chem., 361(12):1787-1794(1980).

[0291] We herein describe the identification and characterization ofnovel polypeptides having homology to snake venom protein A, designatedherein as PRO1186 polypeptides.

[0292] 116. PRO1198

[0293] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1198 polypeptides.

[0294] 117. PRO1158

[0295] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel transmembrane proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1158 polypeptides.

[0296] 118. PRO1159

[0297] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1159 polypeptides.

[0298] 119. PRO1124

[0299] Ion channels are considered to be the gateway to the finalfrontier, the brain. Ion channels and the receptors which control thesechannels are responsible for the passage of ions, or nerve impulses tobe communicated from cell to cell, thus, ion channels are responsiblefor communication. In addition to their critical role in the brain, ionchannels play a critical role in the heart as well as blood pressure.Ion channels have also been linked to other important bodily functionsand conditions, as well as disorders, such as cystic fibrosis. For allof these reasons, ion channels, such as sodium, potassium and chloridechannels, as well as all of their related proteins and receptors are ofinterest. For example, it has been reported that cystic fibrosis resultsfrom a defect in the chloride channel protein, cystic fibrosistransmembrane conductance regulator. McGill, et al., Dig. Dis. Sci.,41(3):540-542 (1996). Chloride channels are further described in atleast Finn, et al., PNAS USA, 90(12):5691-569 (1993) and Finn, et al.,Mol. Cell Biochem., 114(1-2):21-26 (1992).

[0300] Also of interest are molecules related to adhesion molecules, asadhesion molecules are known to be involved in cell-cell signaling andinteractions. More generally, all novel membrane bound-proteins are ofinterest. Membrane-bound proteins and receptors can play an importantrole in the formation, differentiation and maintenance of multicellularorganisms. The fate of many individual cells, e.g., proliferation,migration, differentiation, or interaction with other cells, istypically governed by information received from other cells and/or theimmediate environment. This information is often transmitted by secretedpolypeptides (for instance, mitogenic factors, survival factors,cytotoxic factors, differentiation factors, neuropeptides, and hormones)which are, in turn, received and interpreted by diverse cell receptorsor membrane-bound proteins. Such membrane-bound proteins and cellreceptors include, but are not limited to, cytokine receptors, receptorkinases, receptor phosphatases, receptors involved in cell-cellinteractions, channels, transporters, and cellular adhesin moleculeslike selectins and integrins. For instance, transduction of signals thatregulate cell growth and differentiation is regulated in part byphosphorylation of various cellular proteins. Protein tyrosine kinases,enzymes that catalyze that process, can also act as growth factorreceptors. Examples include fibroblast growth factor receptor and nervegrowth factor receptor.

[0301] Membrane-bound proteins include those which are bound to theouter membrane and intracellular membranes and organelles.Membrane-bound proteins and receptor molecules have various industrialapplications, including as pharmaceutical and diagnostic agents.Receptor immunoadhesins, for instance, can be employed as therapeuticagents to block receptor-ligand interaction. The membrane-bound proteinscan also be employed for screening of potential peptide or smallmolecule inhibitors of the relevant receptor/ligand interaction.

[0302] Efforts are being undertaken by both industry and academia toidentify new, native receptor proteins. Many efforts are focused on thescreening of mammalian recombinant DNA libraries to identify the codingsequences for novel receptor proteins. Herein is presented a polypeptideand nucleic acid encoding therefor which has sequence identity with achloride channel protein chloride channel protein and lung-endothelialcell adhesion molecule-1 (ECAM-1).

[0303] 120. PRO1287

[0304] Fringe is a protein which specifically blocks serrate-mediatedactivation of notch in the dorsal compartment of the Drosophila wingimaginal disc. Fleming et al., Development, 124(15):2973-81 (1997).Therefore, fringe protein is of interest for both its role indevelopment as well as its ability to regulate serrate, particularlyserrate's signaling abilities. Also of interest are novel polypeptideswhich may have a role in development and/or the regulation ofserrate-like molecules. Of particular interest are novel polypeptideshaving homology to fringe.

[0305] We herein describe the identification and characterization ofnovel polypeptides having homology to fringe protein, designated hereinas PRO1287 polypeptides.

[0306] 121. PRO1312

[0307] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel transmembrane proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1312 polypeptides.

[0308] 122. PRO1192

[0309] Membrane-bound proteins of myelin are of interest because oftheir possible implications in various nervous system disordersassociated with improper myelination. Myelin is a cellular sheath,formed by glial cells, that surrounds axons and axonal processes thatenhances various electrochemical properties and provides trophic supportto the neuron. Myelin is formed by Schwann cells in the peripheralnervous system (PNS) and by oligodendrocytes in the central nervoussystem (CNS). Improper myelination of central and peripheral neuronsoccurs in a number of pathologies and leads to improper signalconduction within the nervous systems. Among the various demyelinatingdiseases Multiple Sclerosis is the most notable.

[0310] The predominant integral membrane protein of the CNS myelin ofamphibians, reptiles, birds and mammals are proteolipid protein (PLP)and P0, the main glycoprotein in PNS myelin. (Schlieess and Stoffel,Biol. Chem. Hoppe Seyler (1991) 372(9):865-874). In view of theimportance of membrane-bound proteins of the myelin, efforts are beingundertaken by both industry and academia to identify and characterizevarious myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995)64(6):2427-2436).

[0311] 123. PRO1160

[0312] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1160 polypeptides.

[0313] 124. PRO1187

[0314] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1187 polypeptides.

[0315] 125. PRO1185

[0316] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1185 polypeptides.

[0317] 126. PRO345

[0318] Human tetranectin is a 202 amino acid protein encoded by a genespanning approximately 12 kbp of DNA (Berglund et al., FEBS Lett.309:15-19 (1992)). Tetranectin has been shown to be expressed in avariety of tissues and functions primarily as a plasminogen bindingprotein. Tetranectin has been classified in a distinct group of theC-type lectin superfamily but has structural and possibly functionalsimilarity to the collectin proteins (Nielsen et al., FEBS Lett.412(2):388-396 (1997)). Recent studies have reported that variability inserum tetranectin levels may be predictive of the presence of varioustypes of cancers including, for example, ovarian and colorectal cancers(Hogdall et al., Acta Oncol. 35:63-69 (1996), Hogdall et al., Eur. J.Cancer 3 1A(6):888-894 (1995) and Tuxen et al., Cancer Treat. Rev.21(3):215-245 (1995)). As such, there is significant interest inidentifying and characterizing novel polypeptides having structural andfunctional similarity to the tetranectin protein.

[0319] We herein describe the identification and characterization ofnovel polypeptides having homology to tetranectin protein, designatedherein as PRO1345 polypeptides.

[0320] 127. PRO1245

[0321] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1245 polypeptides.

[0322] 128. PRO358

[0323] Serine protease inhibitors are of interest because they inhibitcatabolism and are sometimes associated with regeneration of tissue. Forexample, a gene encoding a plasma protein associated with liverregeneration has been cloned and termed regeneration-associated serpin-1(RASP-1). New, et al., Biochem. Biophys. Res. Commun., 223(2):404412(1996). While serine protease inhibitors are of interest, particularlyof interest are those which have sequence identity with known serineprotease inhibitors such as RASP-1.

[0324] We herein describe the identification and characterization ofnovel polypeptides having homology to RASP-1, designated herein asPRO1245 polypeptides.

[0325] 129. PRO1195

[0326] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel secreted proteins. We hereindescribe the identification and characterization of novel secretedpolypeptides, designated herein as PRO1195 polypeptides.

[0327] 130. PRO1270

[0328] The recognition of carbohydrates by lectins has been found toplay an important role in various aspects of eukaryotic physiology. Anumber of different animal and plant lectin families exist, but it isthe calcium dependent, or type C, lectins that have recently garneredthe most attention. For example, the recognition of carbohydrateresidues on either endothelial cells or leukocytes by the selectinfamily of calcium dependent lectins has been found to be of profoundimportance to the trafficking of leukocytes to inflammatory sites.Lasky, L., Ann. Rev. Biochem., 64 113-139 (1995). The biophysicalanalysis of these adhesive interactions has suggested thatlectin-carbohydrate binding evolved in this case to allow for theadhesion between leukocytes and the endothelium under the high shearconditions of the vasculature. Thus, the rapid on rates of carbohydraterecognition by such lectins allows for a hasty acquisition of ligand, anecessity under the high shear of the vascular flow. The physiologicaluse of type C lectins in this case is also supported by the relativelylow affinities of these interactions, a requirement for the leukocyterolling phenomenon that has been observed to occur at sites of acuteinflammation. The crystal structures of the mannose binding protein(Weis et al., Science 254, 1608-1615 [1991]; Weis et al., Nature 360127-134 [1992]) and E-selectin (Graves et al., Nature 367(6463), 532-538[1994]), together with various mutagenesis analyses (Erbe et al., J.Cell. Biol. 119(1), 215-227 [1992]; Drickamer, Nature 360, 183-186[1992]; Iobstet al., J. Biol. Chem. 169(22), 15505-15511 [1994]; Koganet al., J. Biol. Chem. 270(23), 14047-14055 [1995]), is consistent withthe supposition that the type C lectins are, in general, involved withthe rapid recognition of clustered carbohydrates. Together, these datasuggest that type C lectins perform a number of critical physiologicalphenomena through the rapid, relatively low affinity recognition ofcarbohydrates.

[0329] Given the obvious importance of the lectin proteins in numerousbiological processes, efforts are currently being made to identify novellectin proteins or proteins having sequence homology to lectin proteins.We herein describe the identification and characterization of novelpolypeptides having homology to a lectin protein, designated herein asPRO1270 polypeptides.

[0330] 131. PRO1271

[0331] Efforts are being undertaken by both industry and academia toidentify new, native membrane-bound proteins. Many of these efforts arefocused on the screening of mammalian recombinant DNA libraries toidentify the coding sequences for novel transmembrane proteins. Weherein describe the identification and characterization of noveltransmembrane polypeptides, designated herein as PRO1271 polypeptides.

[0332] 132. PRO1375

[0333] The proteins L1CAM, G6PD and P55 are each associated with variousknown disease states. Thus, the genomic loci of Fugu rubripes homologsof the human disease genes LICAM, G6PD and P55 were analyzed. Thisanalysis led to the the identification of putative protein 2 (PUT2),GENBANK locus AF026198, accession AF026198. (See GENBANK submissiondata). Thus, PUT2 and proteins which have sequence identity with PUT2,are of interest.

[0334] 133. PRO1385

[0335] Efforts are being undertaken by both industry and academia toidentify new, native secreted proteins.

[0336] Many of these efforts are focused on the screening of mammalianrecombinant DNA libraries to identify the coding sequences for novelsecreted proteins. We herein describe the identification andcharacterization of novel secreted polypeptides, designated herein asPRO1385 polypeptides.

[0337] 134. PRO1387

[0338] Membrane-bound proteins of myelin are of interest because oftheir possible implications in various nervous system disordersassociated with improper myelination. Myelin is a cellular sheath,formed by glial cells, that surrounds axons and axonal processes thatenhances various electrochemical properties and provides trophic supportto the neuron. Myelin is formed by Schwann cells in the peripheralnervous system (PNS) and by oligodendrocytes in the central nervoussystem (CNS). Improper myelination of central and peripheral neuronsoccurs in a number of pathologies and leads to improper signalconduction within the nervous systems. Among the various demyelinatingdiseases Multiple Sclerosis is the most notable.

[0339] The predominant integral membrane protein of the CNS myelin ofamphibians, reptiles, birds and mammals are proteolipid protein (PLP)and P0, the main glycoprotein in PNS myelin. (Schlieess and Stoffel,Biol. Chem. Hoppe Seyler (1991) 372(9):865-874). In view of theimportance of membrane-bound proteins of the myelin, efforts are beingundertaken by both industry and academia to identify and characterizevarious myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995)64(6):2427-2436).

[0340] We herein describe the identification and characterization ofnovel polypeptides having homology to myelin protein, designated hereinas PRO1387 polypeptides.

[0341] 135. PRO1384

[0342] One class of receptor proteins that has been of interest is theNKG2 family of type II transmembrane molecules that are expressed innatural killer cells. These proteins, which have been shown to becovalently associated with CD94, are involved in natural killercell-mediated recognition of different HLA-allotypes (Plougastel, B. etal., Eur. J. Immunol. (1997)27(11):2835-2839), and interact with majorhistocompatibility complex (MHC) class I to either inhibit or activatefunctional activity (Ho, EL. et al., Proc. Natl. Acad. Sci. (1998)95(11):6320-6325). Accordingly, the identification and characterizationof new members of this family of receptor proteins is of interest (seeHouchins J P, et al. J. Exp. Med. (1991) 173(4): 1017-1020).

SUMMARY OF THE INVENTION

[0343] 1. PRO281

[0344] A cDNA clone (DNA16422-1209) has been identified, having homologyto nucleic acid encoding testis enhanced gene transcript (TEGT) proteinthat encodes a novel polypeptide, designated in the present applicationas “PRO281”.

[0345] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO281 polypeptide.

[0346] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO281 polypeptide having the sequence of amino acidresidues from about 1 or about 15 to about 345, inclusive of FIG. 2 (SEQID NO:2), or (b) the complement of the DNA molecule of (a).

[0347] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO281 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 80 orabout 122 and about 1114, inclusive, of FIG. 1 (SEQ ID NO:1).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0348] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209929 (DNA16422-1209) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209929 (DNA16422-1209).

[0349] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 15 to about 345, inclusive of FIG. 2 (SEQID NO:2), or (b) the complement of the DNA of (a).

[0350] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO281 polypeptide having the sequence of amino acid residuesfrom 1 or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, prefereably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0351] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO281 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 14 in thesequence of FIG. 2 (SEQ ID NO:2). The multiple transmembrane domainshave been tentatively identified as extending from about amino acidposition 83 to about amino acid position 105, from about amino acidposition 126 to about amino acid position 146, from about amino acidposition 158 to about amino acid position 177, from about amino acidposition 197 to about amino acid position 216, from about amino acidposition 218 to about amino acid position 238, from about amino acidposition 245 to about amino acid position 265, and from about amino acidposition 271 to about amino acid position 290 in the PRO281 amino acidsequence (FIG. 2, SEQ ID NO:2).

[0352] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or (b) thecomplement of the DNA of (a).

[0353] Another embodiment is directed to fragments of a PRO281polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 1 (SEQ ID NO:1).

[0354] In another embodiment, the invention provides isolated PRO281polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0355] In a specific aspect, the invention provides isolated nativesequence PRO281 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 15 to about 345 ofFIG. 2 (SEQ ID NO:2).

[0356] In another aspect, the invention concerns an isolated PRO281polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2).

[0357] In a further aspect, the invention concerns an isolated PRO281polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2).

[0358] In yet another aspect, the invention concerns an isolated PRO281polypeptide, comprising the sequence of amino acid residues 1 or about15 to about 345, inclusive of FIG. 2 (SEQ ID NO:2), or a fragmentthereof sufficient to provide a binding site for an anti-PRO281antibody. Preferably, the PRO281 fragment retains a qualitativebiological activity of a native PRO281 polypeptide.

[0359] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO281 polypeptide havingthe sequence of amino acid residues from about 1 or about 15 to about345, inclusive of FIG. 2 (SEQ ID NO:2), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0360] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO281 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO281 antibody.

[0361] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO281 polypeptide bycontacting the native PRO281 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0362] In a still further embodiment, the invention concerns acomposition comprising a PRO281 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0363] 2. PRO276

[0364] A cDNA clone (DNA16435-1208) has been identified that encodes anovel polypeptide having two transmembrane domains and designated in thepresent application as “PRO276.”

[0365] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO276 polypeptide.

[0366] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO276 polypeptide having the sequence of amino acidresidues from about 1 to about 251, inclusive of FIG. 4 (SEQ ID NO:6),or (b) the complement of the DNA molecule of (a).

[0367] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO276 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 180 andabout 932, inclusive, of FIG. 3 (SEQ ID NO:5). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

[0368] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209930 (DNA16435-1208), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209930 (DNA16435-1208).

[0369] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 251, inclusive of FIG. 4 (SEQID NO:6), or the complement of the DNA of (a).

[0370] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO276 polypeptide having the sequence of amino acid residues from about1 to about 251, inclusive of FIG. 4 (SEQ ID NO:6), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[0371] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO276 polypeptide in itssoluble, i.e. transmembrane domains deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. Thetransmembrane domains are at about amino acids 98-116 and 152-172.

[0372] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 251, inclusive of FIG. 4 (SEQ ID NO:6), or (b) the complementof the DNA of (a).

[0373] Another embodiment is directed to fragments of a PRO276polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0374] In another embodiment, the invention provides isolated PRO276polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0375] In a specific aspect, the invention provides isolated nativesequence PRO276 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 251 of FIG. 4 (SEQ ID NO:6).

[0376] In another aspect, the invention concerns an isolated PRO276polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 251, inclusive of FIG. 4 (SEQ ID NO:6).

[0377] In a further aspect, the invention concerns an isolated PRO276polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 251 of FIG. 4 (SEQ ID NO:6).

[0378] In yet another aspect, the invention concerns an isolated PRO276polypeptide, comprising the sequence of amino acid residues 1 to about251, inclusive of FIG. 4 (SEQ ID NO:6), or a fragment thereof sufficientto provide a binding site for an anti-PRO276 antibody. Preferably, thePRO276 fragment retains a qualitative biological activity of a nativePRO276 polypeptide.

[0379] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO276 polypeptide havingthe sequence of amino acid residues from about 1 to about 251, inclusiveof FIG. 4 (SEQ ID NO:6), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0380] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO276 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO276 antibody.

[0381] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO276 polypeptide, bycontacting the native PRO276 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0382] In a still further embodiment, the invention concerns acomposition comprising a PRO276 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0383] 3. PRO189

[0384] A cDNA clone (DNA21624-1391) has been identified that encodes anovel polypeptide, designated in the present application as “PRO189”.PRO189 polypeptides have a cytosolic fatty-acid binding domain.

[0385] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO189 polypeptide.

[0386] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO189 polypeptide having the sequence of amino acidresidues from about 1 to about 367, inclusive of FIG. 6 (SEQ ID NO:8),or (b) the complement of the DNA molecule of (a).

[0387] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO189 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 200 andabout 1300, inclusive, of FIG. 5 (SEQ ID NO:7). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0388] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209917 (DNA21624-1391), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209917 (DNA21624-1391).

[0389] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 367, inclusive of FIG. 6 (SEQID NO:8), or the complement of the DNA of (a).

[0390] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO189polypeptide having the sequence of amino acid residues from about 1 toabout 367, inclusive of FIG. 6 (SEQ ID NO:8), or (b) the complement ofthe DNA molecule of (a), and, if the DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[0391] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 367, inclusive of FIG. 6 (SEQ ID NO:8), or (b) the complementof the DNA of (a).

[0392] In another embodiment, the invention provides isolated PRO189polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0393] In a specific aspect, the invention provides isolated nativesequence PRO189 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 367 of FIG. 6 (SEQ ID NO:8).

[0394] In another aspect, the invention concerns an isolated PRO189polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 367, inclusive of FIG. 6 (SEQ ID NO:8).

[0395] Ina further aspect, the invention concerns an isolated PRO189polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 367 of FIG. 6 (SEQ ID NO:8).

[0396] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO189 polypeptide havingthe sequence of amino acid residues from about 1 to about 367, inclusiveof FIG. 6 (SEQ ID NO:8), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0397] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO189 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO189 antibody.

[0398] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO189 polypeptide, bycontacting the native PRO189 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0399] In a still further embodiment, the invention concerns acomposition comprising a PRO189 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0400] 4. PRO190

[0401] Applicants have identified a cDNA clone that encodes a novelpolypeptide having seven transmembrane domains and having sequenceidentity with CMP-sialic acid and UDP-galactose transporters, whereinthe polypeptide is designated in the present application as “PRO190”.

[0402] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO190 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO190polypeptide having amino acid residues 1 through 424 of FIG. 9 (SEQ IDNO:14), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. The isolated nucleic acid sequence maycomprise the cDNA insert of the vector deposited on Jun. 2, 1998 withthe ATCC as DNA23334-1392 which includes the nucleotide sequenceencoding PRO190.

[0403] In another embodiment, the invention provides isolated PRO190polypeptide. In particular, the invention provides isolated nativesequence PRO190 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 424 of FIG. 9 (SEQ IDNO:14). An additional embodiment of the present invention is directed toan isolated PRO190 polypeptide, excluding the transmembrane domains.Optionally, the PRO190 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of the vectordeposited on Jun. 2, 1998 with the ATCC as DNA23334-1392.

[0404] In another embodiment, the invention provides an expressedsequence tag (EST) comprising the nucleotide sequence of SEQ ID NO:15.

[0405] 5. PRO341

[0406] A cDNA clone (DNA26288-1239) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO341”.

[0407] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO341 polypeptide.

[0408] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO341 polypeptide having the sequence of amino acidresidues from about 1 or about 18 to about 458, inclusive of FIG. 12(SEQ ID NO:20), or (b) the complement of the DNA molecule of (a).

[0409] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO341 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 380 orabout 431 and about 1753, inclusive, of FIG. 11 (SEQ ID NO:19).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0410] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209792 (DNA26288-1239) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209792 (DNA26288-1239).

[0411] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 18 to about 458, inclusive of FIG. 12(SEQ ID NO:20), or (b) the complement of the DNA of (a).

[0412] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 165 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO341 polypeptide having the sequence of aminoacid residues from 1 or about 18 to about 458, inclusive of FIG. 12 (SEQID NO:20), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[0413] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO341 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 17 in thesequence of FIG. 12 (SEQ ID NO:20). The transmembrane domains have beententatively identified as extending from about amino acid position 171to about amino acid position 190, from about amino acid position 220 toabout amino acid position 239, from about amino acid position 259 toabout amino acid position 275, from about amino acid position 286 toabout amino acid position 305, from about amino acid position 316 toabout amino acid position 335, from about amino acid position 353 toabout amino acid position 378 and from about amino acid position 396 toabout amino acid position 417 in the PRO341 amino acid sequence (FIG.12, SEQ ID NO:20).

[0414] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20), or (b)the complement of the DNA of (a).

[0415] Another embodiment is directed to fragments of a PRO341polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 11 (SEQ ID NO:19).

[0416] In another embodiment, the invention provides isolated PRO341polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0417] In a specific aspect, the invention provides isolated nativesequence PRO341 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 18 to about 458 ofFIG. 12 (SEQ ID NO:20).

[0418] In another aspect, the invention concerns an isolated PRO341polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20).

[0419] In a further aspect, the invention concerns an isolated PRO341polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20).

[0420] In yet another aspect, the invention concerns an isolated PRO341polypeptide, comprising the sequence of amino acid residues 1 or about18 to about 458, inclusive of FIG. 12 (SEQ ID NO:20), or a fragmentthereof sufficient to provide a binding site for an anti-PRO341antibody. Preferably, the PRO341 fragment retains a qualitativebiological activity of a native PRO341 polypeptide.

[0421] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO341 polypeptide havingthe sequence of amino acid residues from about 1 or about 18 to about458, inclusive of FIG. 12 (SEQ ID NO:20), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0422] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA12920 comprising thenucleotide sequence of SEQ ID NO:21 (see FIG. 13).

[0423] 6. PRO180

[0424] A cDNA clone (DNA26843-1389) has been identified that encodes anovel polypeptide having multiple transmembrane domains designated inthe present application as “PRO180”.

[0425] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO180 polypeptide.

[0426] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO180 polypeptide having the sequence of amino acidresidues from about 1 to about 266, inclusive of FIG. 15 (SEQ ID NO:23),or (b) the complement of the DNA molecule of (a).

[0427] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO180 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 121 andabout 918, inclusive, of FIG. 14 (SEQ ID NO:22). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0428] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203099 (DNA26843-1389), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203099 (DNA26843-1389).

[0429] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 266, inclusive of FIG. 15 (SEQID NO:23), or the complement of the DNA of (a).

[0430] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO180 polypeptide having the sequence of amino acid residues from about1 to about 266, inclusive of FIG. 15 (SEQ ID NO:23), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0431] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO180 polypeptide in itssoluble form, i.e. transmembrane domains deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The transmembrane domains are shown in FIG. 15. It is believed thatPRO180 has a type II transmembrane domain from about amino acids 13-33of SEQ ID NO:23.

[0432] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 266, inclusive of FIG. 15 (SEQ ID NO:23), or (b) the complementof the DNA of (a).

[0433] Another embodiment is directed to fragments of a PRO180polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0434] In another embodiment, the invention provides isolated PRO180polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0435] In a specific aspect, the invention provides isolated nativesequence PRO180 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 266 of FIG. 15 (SEQ IDNO:23).

[0436] In another aspect, the invention concerns an isolated PRO180polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 266, inclusive of FIG. 15 (SEQ ID NO:23).

[0437] In a further aspect, the invention concerns an isolated PRO180polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 266 of FIG. 15 (SEQ ID NO:23).

[0438] In yet another aspect, the invention concerns an isolated PRO180polypeptide, comprising the sequence of amino acid residues 1 to about266, inclusive of FIG. 15 (SEQ ID NO:23), or a fragment thereofsufficient to provide a binding site for an anti-PRO180 antibody.Preferably, the PRO180 fragment retains a qualitative biologicalactivity of a native PRO180 polypeptide.

[0439] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO180 polypeptide havingthe sequence of amino acid residues from about 1 to about 266, inclusiveof FIG. 15 (SEQ ID NO:23), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0440] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO180 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO180 antibody.

[0441] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO180 polypeptide, bycontacting the native PRO180 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0442] In a still further embodiment, the invention concerns acomposition comprising a PRO180 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0443] In another embodiment, the invention provides an expressedsequence tag (EST) (DNA12922) comprising the nucleotide sequence of FIG.16 (SEQ ID NO:24).

[0444] 7. PRO194

[0445] Applicants have identified a cDNA clone that encodes a noveltransmembrane polypeptide, wherein the polypeptide is designated in thepresent application as “PRO194”.

[0446] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO194 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO194polypeptide having amino acid residues 1 to 264 of FIG. 18 (SEQ IDNO:28), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO194 polypeptide having amino acidresidues about 18 to 264 of FIG. 18 (SEQ ID NO:28) or amino acid 1 orabout 18 to X of FIG. 18 (SEQ ID NO:28), where X is any amino acid from96 to 105 of FIG. 18 (SEQ ID NO:28), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA26844-1394 vector deposited on Jun. 2, 1998 as ATCC 209926 whichincludes the nucleotide sequence encoding PRO194.

[0447] In another embodiment, the invention provides isolated PRO194polypeptide. In particular, the invention provides isolated nativesequence PRO194 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 264 of FIG. 18 (SEQ ID NO:28).Additional embodiments of the present invention are directed to PRO194polypeptides comprising amino acids about 18 to 264 of FIG. 18 (SEQ IDNO:28) or amino acid 1 or about 18 to X of FIG. 18 (SEQ ID NO:28), whereX is any amino acid from 96 to 105 of FIG. 18 (SEQ ID NO:28).Optionally, the PRO194 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA26844-1394 vector deposited on Jun. 2, 1998 as ATCC 209926.

[0448] 8. PRO203

[0449] Applicants have identified a cDNA clone that encodes a novelpolypeptide having sequence identity to glutathione-S-transferase,wherein the polypeptide is designated in the present application as“PRO203”.

[0450] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO203 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO203polypeptide having amino acid residues 1 to 347 of FIG. 20 (SEQ IDNO:30), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO203 polypeptide having amino acidresidues X to 347 of FIG. 20 (SEQ ID NO:30), where X is any amino acidfrom 83 to 92 of FIG. 20 (SEQ ID NO:30), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA30862-1396 vector deposited on Jun. 2, 1998, as ATCC 209920 whichincludes the nucleotide sequence encoding PRO203.

[0451] In another embodiment, the invention provides isolated PRO203polypeptide. In particular, the invention provides isolated nativesequence PRO203 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 347 of FIG. 20 (SEQ ID NO:30).Additional embodiments of the present invention are directed to PRO203polypeptides comprising amino acid X to 347 of FIG. 20 (SEQ ID NO:30),where X is any amino acid from 83 to 92 of FIG. 20 (SEQ ID NO:30).Optionally, the PRO203 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA30862-1396 vector deposited on Jun. 2, 1998, as ATCC 209920.

[0452] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA15618 which comprises thenucleotide sequence of FIG. 21 (SEQ ID NO:31). 9. PRO290

[0453] A cDNA clone (DNA35680-1212) has been identified which encodes apolypeptide designated in the present application as “PRO290.” PRO290polypeptides have sequence identity with NTII-1, FAN and beige.

[0454] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO290 polypeptide.

[0455] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO290 polypeptide having the sequence of amino acidresidues from about 1 to about 1003, inclusive of FIG. 23 (SEQ IDNO:33), or (b) the complement of the DNA molecule of (a).

[0456] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO290 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 293 andabout 3301, inclusive, of FIG. 22 (SEQ ID NO:32). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0457] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209790 (DNA35680-1212), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209790 (DNA35680-1212).

[0458] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 1003, inclusive of FIG. 23(SEQ ID NO:33), or the complement of the DNA of (a).

[0459] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO290polypeptide having the sequence of amino acid residues from about 1 toabout 1003, inclusive of FIG. 23 (SEQ ID NO:33), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[0460] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 1003, inclusive of FIG. 23 (SEQ ID NO:33), or (b) thecomplement of the DNA of (a).

[0461] In another embodiment, the invention provides isolated PRO290polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0462] In a specific aspect, the invention provides isolated nativesequence PRO290 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 1003 of FIG. 23 (SEQ IDNO:33).

[0463] In another aspect, the invention concerns an isolated PRO290polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 1003, inclusive of FIG. 23 (SEQ ID NO:33).

[0464] In a further aspect, the invention concerns an isolated PRO290polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 1003 of FIG. 23 (SEQ ID NO:33).

[0465] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO290 polypeptide havingthe sequence of amino acid residues from about 1 to about 1003,inclusive of FIG. 23 (SEQ ID NO:33), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0466] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO290 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO290 antibody.

[0467] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO290 polypeptide, bycontacting the native PRO290 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0468] In a still further embodiment, the invention concerns acomposition comprising a PRO290 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0469] 10. PRO874

[0470] Applicants have identified a cDNA clone that encodes a novelmulti-span transmembrane polypeptide, which is designated in the presentapplication as “PRO874”.

[0471] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO874 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO874polypeptide having amino acid residues 1 to 321 of FIG. 25 (SEQ IDNO:36), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO874 polypeptide having amino acidfrom about X to 321 of FIG. 25 (SEQ ID NO:36), where X is any amino acidfrom about 270 to about 279 of FIG. 25 (SEQ ID NO:36), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA40621-1440 vector deposited on Jun. 2, 1998,as ATCC 209922 which includes the nucleotide sequence encoding PRO874.

[0472] In another embodiment, the invention provides isolated PRO874polypeptide. In particular, the invention provides isolated nativesequence PRO874 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 321 of FIG. 25 (SEQ ID NO:36).Additional embodiments of the present invention are directed to PRO874polypeptides comprising amino acids X to 321 of FIG. 25 (SEQ ID NO:36),where X is any amino acid from about 270 to about 279 of FIG. 25 (SEQ IDNO:36). Optionally, the PRO874 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA40621-1440 vector deposited on Jun. 2, 1998, as ATCC 209922.

[0473] 11. PRO710

[0474] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to CDC45 protein, wherein the polypeptide isdesignated in the present application as “PRO710”.

[0475] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO710 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO710polypeptide having amino acid residues 1 to 566 of FIG. 27 (SEQ IDNO:41), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO710 polypeptide having amino acidresidues about 33 to 566 of FIG. 27 (SEQ ID NO:41) or amino acid 1 orabout 33 to X of FIG. 27 (SEQ ID NO:41), where X is any amino acid from449 to 458 of FIG. 27 (SEQ ID NO:41), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907 whichincludes the nucleotide sequence encoding PRO710.

[0476] In another embodiment, the invention provides isolated PRO710polypeptide. In particular, the invention provides isolated nativesequence PRO710 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 566 of FIG. 27 (SEQ ID NO:41).Additional embodiments of the present invention are directed to PRO710polypeptides comprising amino acids about 33 to 566 of FIG. 27 (SEQ IDNO:41) or amino acid 1 or about 33 to X of FIG. 27 (SEQ ID NO:41), whereX is any amino acid from 449 to 458 of FIG. 27 (SEQ ID NO:41).Optionally, the PRO710 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of theDNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907.

[0477] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA38190 comprising thenucleotide sequence of FIG. 28 (SEQ ID NO:42).

[0478] 12. PRO1151

[0479] A cDNA clone (DNA44694-1500) has been identified, having homologyto nucleic acid encoding C1q protein, that encodes a novel polypeptide,designated in the present application as “PRO1151”.

[0480] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1151 polypeptide.

[0481] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1151 polypeptide having the sequence of aminoacid residues from about 1 or about 21 to about 259, inclusive of FIG.30 (SEQ ID NO:47), or (b) the complement of the DNA molecule of (a).

[0482] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1151 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 272 orabout 332 and about 1048, inclusive, of FIG. 29 (SEQ ID NO:46).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0483] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203114 (DNA44694-1500) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203114 (DNA44694-1500).

[0484] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 21 to about 259, inclusive of FIG. 30(SEQ ID NO:47), or (b) the complement of the DNA of (a).

[0485] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1151 polypeptide having the sequence of amino acidresidues from 1 or about 21 to about 259, inclusive of FIG. 30 (SEQ IDNO:47), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[0486] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1151 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 20 in the sequence of FIG.30 (SEQ ID NO:47).

[0487] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47), or (b)the complement of the DNA of (a).

[0488] Another embodiment is directed to fragments of a PRO1151polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 29 (SEQ ID NO:46).

[0489] In another embodiment, the invention provides isolated PRO1151polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0490] In a specific aspect, the invention provides isolated nativesequence PRO1151 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 21 to about 259 ofFIG. 30 (SEQ ID NO:47).

[0491] In another aspect, the invention concerns an isolated PRO1151polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47).

[0492] In a further aspect, the invention concerns an isolated PRO1151polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47).

[0493] In yet another aspect, the invention concerns an isolated PRO1151polypeptide, comprising the sequence of amino acid residues 1 or about21 to about 259, inclusive of FIG. 30 (SEQ ID NO:47), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1151antibody. Preferably, the PRO1151 fragment retains a qualitativebiological activity of a native PRO1151 polypeptide.

[0494] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1151 polypeptide havingthe sequence of amino acid residues from about 1 or about 21 to about259, inclusive of FIG. 30 (SEQ ID NO:47), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0495] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1151 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1151 antibody.

[0496] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1151 polypeptide bycontacting the native PRO1151 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0497] In a still further embodiment, the invention concerns acomposition comprising a PRO1151 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0498] 13. PRO1282

[0499] A cDNA clone (DNA45495-1550) has been identified that encodes anovel polypeptide having sequence identity with leucine rich repeatproteins and designated in the present application as “PRO1282.”

[0500] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1282 polypeptide.

[0501] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1282 polypeptide having the sequence of aminoacid residues from about 24 to about 673, inclusive of FIG. 32 (SEQ IDNO:52), or (b) the complement of the DNA molecule of (a).

[0502] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1282 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 189 andabout 2138, inclusive, of FIG. 31 (SEQ ID NO:51). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0503] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203156 (DNA45495-1550), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203156 (DNA45495-1550).

[0504] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 24 to about 673, inclusive of FIG. 32(SEQ ID NO:52), or the complement of the DNA of (a).

[0505] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1282 polypeptide having the sequence of amino acid residues fromabout 24 to about 673, inclusive of FIG. 32 (SEQ ID NO:52), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0506] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1282 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 23 in thesequence of FIG. 32 (SEQ ID NO:52). The transmembrane domain has beententatively identified as extending from about amino acid position 579through about amino acid position 599 in the PRO1282 amino acid sequence(FIG. 32, SEQ ID NO:52).

[0507] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 24to about 673, inclusive of FIG. 32 (SEQ ID NO:52), or (b) the complementof the DNA of (a).

[0508] Another embodiment is directed to fragments of a PRO1282polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0509] In another embodiment, the invention provides isolated PRO1282polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0510] In a specific aspect, the invention provides isolated nativesequence PRO1282 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 24 through 673 of FIG. 32 (SEQ IDNO:52).

[0511] In another aspect, the invention concerns an isolated PRO1282polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues24 to about 673, inclusive of FIG. 32 (SEQ ID NO:52).

[0512] In a further aspect, the invention concerns an isolated PRO1282polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 24through 673 of FIG. 32 (SEQ ID NO:52).

[0513] In yet another aspect, the invention concerns an isolated PRO1282polypeptide, comprising the sequence of amino acid residues 24 to about673, inclusive of FIG. 32 (SEQ ID NO:52), or a fragment thereofsufficient to provide a binding site for an anti-PRO1282 antibody.Preferably, the PRO1282 fragment retains a qualitative biologicalactivity of a native PRO1282 polypeptide.

[0514] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1282 polypeptide havingthe sequence of amino acid residues from about 24 to about 673,inclusive of FIG. 32 (SEQ ID NO:52), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0515] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1282 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1282 antibody.

[0516] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1282 polypeptide, bycontacting the native PRO1282 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0517] In a still further embodiment, the invention concerns acomposition comprising a PRO1282 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0518] 14. PRO358

[0519] Applicants have identified a novel cDNA clone that encodes novelhuman Toll polypeptides, designated in the present application asPRO358.

[0520] In one embodiment, the invention provides an isolated nucleicacid molecule comprising a DNA encoding a polypeptide having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to (a) a DNA moleculeencoding a PRO358 polypeptide having amino acids 20 to 575 of FIG. 34(SEQ ID NO:57), or (b) the complement of the DNA molecule of (a). Thecomplementary DNA molecule preferably remains stably bound to suchencoding nucleic acid sequence under at least moderate, and optionally,under high stringency conditions.

[0521] In a further embodiment, the isolated nucleic acid moleculecomprises a polynucleotide that has at least about 90%, preferably atleast about 95% sequence identity with a polynucleotide encoding apolypeptide comprising the sequence of amino acids 1 to 811 of FIG. 34(SEQ ID NO:57).

[0522] In a specific embodiment, the invention provides an isolatednucleic acid molecule comprising DNA encoding native or variant PRO358polypeptide, with or without the N-terminal signal sequence, and with orwithout the transmembrane regions of the respective full-lengthsequences. In one aspect, the isolated nucleic acid comprises DNAencoding a mature, full-length native PRO358 polypeptide having aminoacid residues 1 to 811 of FIG. 34 (SEQ ID NO:57), or is complementary tosuch encoding nucleic acid sequence. In another aspect, the inventionconcerns an isolated nucleic acid molecule that comprises DNA encoding anative PRO358 polypeptide without an N-terminal signal sequence, or iscomplementary to such encoding nucleic acid sequence. In yet anotherembodiment, the invention concerns nucleic acid encodingtransmembrane-domain deleted or inactivated forms of the full-lengthnative PRO358 protein.

[0523] In another embodiment, the invention provides an isolated nucleicacid molecule which comprises the clone (DNA47361-1249) deposited onNov. 7, 1997, under ATCC number 209431.

[0524] In a specific embodiment, the invention provides a vectorcomprising a polynucleotide having at least about 80% sequence identity,preferably at least about 85% sequence identity, more preferably atleast about 90% sequence identity, most preferably at least about 95%sequence identity with a polynucleotide encoding a polypeptidecomprising the sequence of amino acids 20 to 811 of FIG. 34 (SEQ IDNO:57), or the complement of such polynucleotide. In a particularembodiment, the vector comprises DNA encoding the novel Toll homologue(PRO358), with or without the N-terminal signal sequence (about aminoacids 1 to 19), or a transmembrane-domain (about amino acids 576-595)deleted or inactivated variant thereof, or the extracellular domain(about amino acids 20 to 595) of the mature protein, or a proteincomprising any one of these sequences. A host cell comprising such avector is also provided.

[0525] In another embodiment, the invention provides isolated PRO358polypeptides. The invention further provides an isolated native sequencePRO358 polypeptide, or variants thereof. In particular, the inventionprovides an isolated native sequence PRO358 polypeptide, which incertain embodiments, includes the amino acid sequence comprisingresidues 20 to 575, or 20 to 811, or 1 to 811 of FIG. 34 (SEQ ID NO:57).

[0526] In yet another embodiment, the invention concerns agonists andantagonists of the native PRO358 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO358 antibody.

[0527] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of the native PRO358 polypeptide.

[0528] In a still further embodiment, the invention concerns acomposition comprising a PRO358 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0529] The invention further concerns a composition comprising anantibody specifically binding a PRO358 polypeptide, in combination witha pharmaceutically acceptable carrier.

[0530] The invention also concerns a method of treating septic shockcomprising administering to a patient an effective amount of anantagonist of a PRO358 polypeptide. In a specific embodiment, theantagonist is a blocking antibody specifically binding a native PRO358polypeptide.

[0531] 15. PRO1310

[0532] A cDNA clone (DNA47394-1572) has been identified that encodes anovel polypeptide having sequence identity with carboxypeptidase X2 anddesignated in the present application as “PRO1310.”

[0533] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1310 polypeptide.

[0534] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1310 polypeptide having the sequence of aminoacid residues from about 26 to about 765, inclusive of FIG. 36 (SEQ IDNO:62), or (b) the complement of the DNA molecule of (a).

[0535] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1310 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 401 andabout 2593, inclusive, of FIG. 35 (SEQ ID NO:61). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0536] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203109 (DNA47394-1572), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203109 (DNA47394-1572).

[0537] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 26 to about 765, inclusive of FIG. 36(SEQ ID NO:62), or the complement of the DNA of (a).

[0538] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1310 polypeptide having the sequence of amino acid residues fromabout 26 to about 765, inclusive of FIG. 36 (SEQ ID NO:62), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0539] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 26to about 765, inclusive of FIG. 36 (SEQ ID NO:62), or (b) the complementof the DNA of (a).

[0540] In another embodiment, the invention provides isolated PRO1310polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0541] In a specific aspect, the invention provides isolated nativesequence PRO1310 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 26 through 765 of FIG. 36 (SEQ IDNO:62).

[0542] In another aspect, the invention concerns an isolated PRO1310polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues26 to about 765, inclusive of FIG. 36 (SEQ ID NO:62).

[0543] In a further aspect, the invention concerns an isolated PRO1310polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 26through 765 of FIG. 36 (SEQ ID NO:62).

[0544] In yet another aspect, the invention concerns an isolated PRO1310polypeptide, comprising the sequence of amino acid residues 26 to about765, inclusive of FIG. 36 (SEQ ID NO:62), or a fragment thereofsufficient to provide a binding site for an anti-PRO1310 antibody.Preferably, the PRO1310 fragment retains a qualitative biologicalactivity of a native PRO1310 polypeptide.

[0545] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1310 polypeptide havingthe sequence of amino acid residues from about 26 to about 765,inclusive of FIG. 36 (SEQ ID NO:62), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0546] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1310 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1310 antibody.

[0547] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1310 polypeptide, bycontacting the native PRO1310 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0548] In a still further embodiment, the invention concerns acomposition comprising a PRO1310 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0549] 16. PRO698

[0550] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to olfactomedin, wherein the polypeptide isdesignated in the present application as “PRO698”.

[0551] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO698 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO698polypeptide having amino acid residues 1 to 510 of FIG. 38 (SEQ IDNO:67), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO698 polypeptide having amino acidresidues about 21 to 510 of FIG. 38 (SEQ ID NO:67), or is complementaryto such encoding nucleic acid sequence, and remains stably bound to itunder at least moderate, and optionally, under high stringencyconditions. The isolated nucleic acid sequence may comprise the cDNAinsert of the DNA48320-1433 vector deposited on May 27, 1998 as ATCC209904 which includes the nucleotide sequence encoding PRO698.

[0552] In another embodiment, the invention provides isolated PRO698polypeptide. In particular, the invention provides isolated nativesequence PRO698 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 510 of FIG. 38 (SEQ ID NO:67).Additional embodiments of the present invention are directed to PRO698polypeptides comprising amino acids about 21 to 510 of FIG. 38 (SEQ IDNO:67). Optionally, the PRO698 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904.

[0553] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA39906 comprising thenucleotide sequence of FIG. 39 (SEQ ID NO:68).

[0554] 17. PRO732

[0555] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to the human placental protein Diff33,wherein the polypeptide is designated in the present application as“PRO732 ”.

[0556] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO732 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO732polypeptide having amino acid residues 1 to 453 of FIG. 41 (SEQ IDNO:73), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO732 polypeptide having amino acidresidues about 29 to 453 of FIG. 41 (SEQ ID NO:73) or amino acid 1 orabout 29 to X of FIG. 41 (SEQ ID NO:73), where X is any amino acid from31 to 40 of FIG. 41 (SEQ ID NO:73), or is complementary to such encodingnucleic acid sequence, and remains stably bound to it under at leastmoderate, and optionally, under high stringency conditions. The isolatednucleic acid sequence may comprise the cDNA insert of the DNA48334-1435vector deposited on Jun. 2, 1998 as ATCC 209924 which includes thenucleotide sequence encoding PRO732.

[0557] In another embodiment, the invention provides isolated PRO732polypeptide. In particular, the invention provides isolated nativesequence PRO732 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 453 of FIG. 41 (SEQ ID NO:73).Additional embodiments of the present invention are directed to PRO732polypeptides comprising amino acids about 29 to 453 of FIG. 41 (SEQ IDNO:73) or amino acid 1 or about 29 to X of FIG. 41 (SEQ ID NO:73), whereX is any amino acid from 31 to 40 of FIG. 41 (SEQ ID NO:73). Optionally,the PRO732 polypeptide is obtained or is obtainable by expressing thepolypeptide encoded by the cDNA insert of the DNA48334-1435 vectordeposited on Jun. 2, 1998 as ATCC 209924.

[0558] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA20239 comprising thenucleotide sequence of FIG. 42 (SEQ ID NO:74).

[0559] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA38050 comprising thenucleotide sequence of FIG. 43 (SEQ ID NO:75).

[0560] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA40683 comprising thenucleotide sequence of FIG. 44 (SEQ ID NO:76).

[0561] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA42580 comprising thenucleotide sequence of FIG. 45 (SEQ ID NO:77).

[0562] 18. PRO1120

[0563] A cDNA clone (DNA48606-1479) has been identified that encodes anovel polypeptide having homology sulfatases, designated in the presentapplication as “PRO1120.”

[0564] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1120 polypeptide.

[0565] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1120 polypeptide having the sequence of aminoacid residues from about 18 to about 867, inclusive of FIG. 47 (SEQ IDNO:84), or (b) the complement of the DNA molecule of (a).

[0566] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1120 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 659 andabout 3208, inclusive, of FIG. 46 (SEQ ID NO:83). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0567] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203040 (DNA48606-1479), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203040 (DNA48606-1479).

[0568] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 18 to about 867, inclusive of FIG. 47(SEQ ID NO:84), or the complement of the DNA of (a).

[0569] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1120 polypeptide having the sequence of amino acid residues fromabout 18 to about 867, inclusive of FIG. 47 (SEQ ID NO:84), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0570] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1120 polypeptide, with orwithout the N-terminal signal sequence, or is complementary to suchencoding nucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 through about aminoacid position 17 in the sequence of FIG. 47 (SEQ ID NO:84).

[0571] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 867, inclusive of FIG. 47 (SEQ ID NO:84), or (b) the complementof the DNA of (a).

[0572] Another embodiment is directed to fragments of a PRO1120polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0573] In another embodiment, the invention provides isolated PRO1120polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0574] In a specific aspect, the invention provides isolated nativesequence PRO1120 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 18 to 867 of FIG. 47 (SEQ ID NO:84).

[0575] In another aspect, the invention concerns an isolated PRO1120polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 867, inclusive of FIG. 47 (SEQ ID NO:84).

[0576] In a further aspect, the invention concerns an isolated PRO1120polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18 to867 of FIG. 47 (SEQ ID NO:84).

[0577] In yet another aspect, the invention concerns an isolated PRO1120polypeptide, comprising the sequence of amino acid residues 18 to about867, inclusive of FIG. 47 (SEQ ID NO:84), or a fragment thereofsufficient to provide a binding site for an anti-PRO1120 antibody.Preferably, the PRO1120 fragment retains a qualitative biologicalactivity of a native PRO1120 polypeptide.

[0578] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1120 polypeptide havingthe sequence of amino acid residues from about 18 to about 867,inclusive of FIG. 47 (SEQ ID NO:84), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0579] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1120 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1120 antibody.

[0580] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1120 polypeptide, bycontacting the native PRO1120 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0581] In a still further embodiment, the invention concerns acomposition comprising a PRO1120 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0582] 19. PRO537

[0583] A cDNA clone (DNA49141-1431) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO537”.

[0584] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO537 polypeptide.

[0585] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO537 polypeptide having the sequence of amino acidresidues from about 1 or about 32 to about 115, inclusive of FIG. 49(SEQ ID NO:95), or (b) the complement of the DNA molecule of (a).

[0586] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO537 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 97 orabout 190 and about 441, inclusive, of FIG. 48 (SEQ ID NO:94).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0587] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203003 (DNA49141-1431) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203003 (DNA49141-1431).

[0588] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 32 to about 115, inclusive of FIG. 49(SEQ ID NO:95), or (b) the complement of the DNA of (a).

[0589] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO537 polypeptide having the sequence of amino acid residuesfrom 1 or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, prefereably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0590] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO537 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 31 in the sequence of FIG.49 (SEQ ID NO:95).

[0591] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or (b)the complement of the DNA of (a).

[0592] Another embodiment is directed to fragments of a PRO537polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 48 (SEQ ID NO:94).

[0593] In another embodiment, the invention provides isolated PRO537polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0594] In a specific aspect, the invention provides isolated nativesequence PRO537 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 32 to about 115 ofFIG. 49 (SEQ ID NO:95).

[0595] In another aspect, the invention concerns an isolated PRO537polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95).

[0596] In a further aspect, the invention concerns an isolated PRO537polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95).

[0597] In yet another aspect, the invention concerns an isolated PRO537polypeptide, comprising the sequence of amino acid residues 1 or about32 to about 115, inclusive of FIG. 49 (SEQ ID NO:95), or a fragmentthereof sufficient to provide a binding site for an anti-PRO537antibody. Preferably, the PRO537 fragment retains a qualitativebiological activity of a native PRO537 polypeptide.

[0598] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO537 polypeptide havingthe sequence of amino acid residues from about 1 or about 32 to about115, inclusive of FIG. 49 (SEQ ID NO:95), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0599] 20. PRO536

[0600] A cDNA clone (DNA49142-1430) has been identified, that encodes anovel secreted polypeptide, designated in the present application as“PRO536”.

[0601] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO536 polypeptide.

[0602] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO536 polypeptide having the sequence of amino acidresidues from about 1 or about 26 to about 313, inclusive of FIG. 51(SEQ ID NO:97), or (b) the complement of the DNA molecule of (a).

[0603] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO536 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 48 orabout 123 and about 986, inclusive, of FIG. 50 (SEQ ID NO:96).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0604] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203002 (DNA49142-1430) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203002 (DNA49142-1430).

[0605] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 26 to about 313, inclusive of FIG. 51(SEQ ID NO:97), or (b) the complement of the DNA of (a).

[0606] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO536 polypeptide having the sequence of amino acid residuesfrom 1 or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, prefereably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0607] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO536 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 25 in the sequence of FIG.51 (SEQ ID NO:97).

[0608] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or (b)the complement of the DNA of (a).

[0609] Another embodiment is directed to fragments of a PRO536polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 50 (SEQ ID NO:96).

[0610] In another embodiment, the invention provides isolated PRO536polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0611] In a specific aspect, the invention provides isolated nativesequence PRO536 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 26 to about 313 ofFIG. 51 (SEQ ID NO:97).

[0612] In another aspect, the invention concerns an isolated PRO536polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97).

[0613] In a further aspect, the invention concerns an isolated PRO536polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97).

[0614] In yet another aspect, the invention concerns an isolated PRO536polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 313, inclusive of FIG. 51 (SEQ ID NO:97), or a fragmentthereof sufficient to provide a binding site for an anti-PRO536antibody. Preferably, the PRO536 fragment retains a qualitativebiological activity of a native PRO536 polypeptide.

[0615] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO536 polypeptide havingthe sequence of amino acid residues from about 1 or about 26 to about313, inclusive of FIG. 51 (SEQ ID NO:97), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0616] 21. PRO535

[0617] A cDNA clone (DNA49143-1429) has been identified, having homologyto nucleic acid encoding a putative peptidyl-prolyl isomerase thatencodes a novel polypeptide, designated in the present application as“PRO535”.

[0618] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO535 polypeptide.

[0619] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO535 polypeptide having the sequence of amino acidresidues from about 1 or about 26 to about 201, inclusive of FIG. 53(SEQ ID NO:99), or (b) the complement of the DNA molecule of (a).

[0620] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO535 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 78 orabout 153 and about 680, inclusive, of FIG. 52 (SEQ ID NO:98).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0621] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203013 (DNA49143-1429) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203013 (DNA49143-1429).

[0622] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 26 to about 201, inclusive of FIG. 53(SEQ ID NO:99), or (b) the complement of the DNA of (a).

[0623] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO535 polypeptide having the sequence of amino acid residuesfrom 1 or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or(b) the complement of the DNA molecule of (a), and, if the DNA moleculehas at least about an 80% sequence identity, prefereably at least aboutan 85% sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0624] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO535 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 25 in thesequence of FIG. 53 (SEQ ID NO:99). The transmembrane domain has beententatively identified as extending from about amino acid position 155to about amino acid position 174 in the PRO535 amino acid sequence (FIG.53, SEQ ID NO:99).

[0625] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or (b)the complement of the DNA of (a).

[0626] Another embodiment is directed to fragments of a PRO535polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 52 (SEQ ID NO:98).

[0627] In another embodiment, the invention provides isolated PRO535polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0628] In a specific aspect, the invention provides isolated nativesequence PRO535 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 26 to about 201 ofFIG. 53 (SEQ ID NO:99).

[0629] In another aspect, the invention concerns an isolated PRO535polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99).

[0630] In a further aspect, the invention concerns an isolated PRO535polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99).

[0631] In yet another aspect, the invention concerns an isolated PRO535polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 201, inclusive of FIG. 53 (SEQ ID NO:99), or a fragmentthereof sufficient to provide a binding site for an anti-PRO535antibody. Preferably, the PRO535 fragment retains a qualitativebiological activity of a native PRO535 polypeptide.

[0632] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO535 polypeptide havingthe sequence of amino acid residues from about 1 or about 26 to about201, inclusive of FIG. 53 (SEQ ID NO:99), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0633] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO535 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO535 antibody.

[0634] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO535 polypeptide bycontacting the native PRO535 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0635] In a still further embodiment, the invention concerns acomposition comprising a PRO535 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0636] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA30861 comprising thenucleotide sequence of FIG. 54 (SEQ ID NO:100).

[0637] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA36351 comprising thenucleotide sequence of FIG. 55 (SEQ ID NO:101).

[0638] 22. PRO718

[0639] Applicants have identified a cDNA clone that encodes a noveltetraspan membrane polypeptide, wherein the polypeptide is designated inthe present application as “PRO718”.

[0640] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO718 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO718polypeptide having amino acid residues 1 to 157 of FIG. 57 (SEQ IDNO:103), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO718 polypeptide having amino acidresidues X to 157 of FIG. 57 (SEQ ID NO:103), where X is any amino acidfrom 143 to 152 of FIG. 57 (SEQ ID NO:103), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA49647-1398 vector deposited on Jun. 2, 1998 as ATCC 209919 whichincludes the nucleotide sequence encoding PRO718.

[0641] In another embodiment, the invention provides isolated PRO718polypeptide. In particular, the invention provides isolated nativesequence PRO718 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 157 of FIG. 57 (SEQ ID NO:103).Additional embodiments of the present invention are directed to isolatedPRO718 polypeptides comprising amino acids X to 157 of FIG. 57 (SEQ IDNO:103), where X is any amino acid from 143 to 152 of FIG. 57 (SEQ IDNO:103). Optionally, the PRO718 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA49647-1398 vector deposited on Jun. 2, 1998 as ATCC 209919.

[0642] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA15386 which comprises thenucleotide sequence of FIG. 58 (SEQ ID NO:104).

[0643] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA16630 which comprises thenucleotide sequence of FIG. 59 (SEQ ID NO:105).

[0644] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA16829 which comprises thenucleotide sequence of FIG. 60 (SEQ ID NO:106).

[0645] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA28357 which comprises thenucleotide sequence of FIG. 61 (SEQ ID NO:107).

[0646] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA43512 which comprises thenucleotide sequence of FIG. 62 (SEQ ID NO:108).

[0647] 23. PRO872

[0648] Applicants have identified a cDNA clone, DNA49819-1439, thatencodes a novel polypeptide having homology to dehydrogenases whereinthe polypeptide is designated in the present application as “PRO872”.

[0649] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO872 polypeptide.

[0650] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO872 polypeptide having the sequence of amino acidresidues from 1 or about 19 to about 610, inclusive of FIG. 64 (SEQ IDNO:113), or (b) the complement of the DNA molecule of (a).

[0651] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO872 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid between about residues68 and about 1843, inclusive of FIG. 63 (SEQ ID NO:112). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0652] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209931 (DNA49819-1439), which was deposited on Jun. 2, 1998.In a preferred embodiment, the nucleic acid comprises a DNA moleculeencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209931 (DNA49819-1439).

[0653] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 19 to about 610, inclusive of FIG. 64(SEQ ID NO:113).

[0654] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO872 extracellular domain(ECD), with or without the N-terminal signal sequence and/or theinitiating methionine, and its soluble variants (i.e. transmembranedomain(s) deleted or inactivated) or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 to about amino acidposition 18 in the sequence of FIG. 64 (SEQ ID NO:113). The firsttransmembrane domain region has been tentatively identified as extendingfrom about amino acid position 70 to about amino acid position 87 in thePRO872 amino acid sequence (FIG. 64, SEQ ID NO:113).

[0655] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 19 to about 610, inclusive of FIG.64 (SEQ ID NO:113).

[0656] Another embodiment is directed to fragments of a PRO872polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[0657] In another embodiment, the invention provides isolated PRO872polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0658] In a specific aspect, the invention provides isolated nativesequence PRO872 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 19 to 610 of FIG. 64 (SEQID NO:113).

[0659] In another aspect, the invention concerns an isolated PRO872polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to 610, inclusive of FIG. 64 (SEQ ID NO:113).

[0660] In a further aspect, the invention concerns an isolated PRO872polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to 610 of FIG. 64 (SEQ ID NO:113).

[0661] In another aspect, the invention concerns a PRO872 extracellulardomain comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to X of FIG. 64 (SEQ ID NO:113), wherein X is any one ofamino acid residues 66 to 75 of FIG. 64 (SEQ ID NO:113).

[0662] In yet another aspect, the invention concerns an isolated PRO872polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 610, inclusive of FIG. 64 (SEQ ID NO:113), or a fragmentthereof sufficient to provide a binding site for an anti-PRO872antibody. Preferably, the PRO872 fragment retains a qualitativebiological activity of a native PRO872 polypeptide.

[0663] In another aspect, the present invention is directed to fragmentsof a PRO872 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[0664] In yet another embodiment, the invention concerns agonist andantagonists of the PRO872 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO872 antibody.

[0665] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO872 polypeptide.

[0666] In still a further embodiment, the invention concerns acomposition comprising a PRO872 polypeptide as hereinabove defined, incombination with a pharmaceutically acceptable carrier. 24. PRO1063

[0667] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to human type IV collagenase, wherein thepolypeptide is designated in the present application as “PRO1063”.

[0668] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1063 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1063polypeptide having amino acid residues 1 to 301 of FIG. 66 (SEQ IDNO:115), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO1063 polypeptide having amino acidresidues about 22 to 301 of FIG. 66 (SEQ ID NO:115), or is complementaryto such encoding nucleic acid sequence, and remains stably bound to itunder at least moderate, and optionally, under high stringencyconditions. The isolated nucleic acid sequence may comprise the cDNAinsert of the DNA49820-1427 vector deposited on Jun. 2, 1998 as ATCC209932 which includes the nucleotide sequence encoding PRO1063.

[0669] In another embodiment, the invention provides isolated PRO1063polypeptide. In particular, the invention provides isolated nativesequence PRO1063 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 301 of FIG. 66 (SEQ ID NO:115).Additional embodiments of the present invention are directed to PRO1063polypeptides comprising amino acids about 22 to 301 of FIG. 66 (SEQ IDNO:115). Optionally, the PRO1063 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA49820-1427 vector deposited on Jun. 2, 1998 as ATCC 209932.

[0670] 25. PRO619

[0671] A cDNA clone (DNA49821-1562) has been identified that encodes anovel polypeptide, designated in the present application as “PRO619.”PRO619 polypeptides have sequence identity with VpreB genes,particularly to VpreB3.

[0672] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO619 polypeptide.

[0673] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO619 polypeptide having the sequence of amino acidresidues from about 1 or 21 to about 123, inclusive of FIG. 68 (SEQ IDNO:117), or (b) the complement of the DNA molecule of (a).

[0674] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO619 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 81 or 141and about 449, inclusive, of FIG. 67 (SEQ ID NO:116). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0675] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209981 (DNA49821-1562), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209981 (DNA49821-1562).

[0676] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 21 to about 123, inclusive of FIG.68 (SEQ ID NO:117), or the complement of the DNA of (a).

[0677] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO619polypeptide having the sequence of amino acid residues from about 1 or21 to about 123, inclusive of FIG. 68 (SEQ ID NO:117), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0678] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO619 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,which is in a soluble form. The signal peptide has been tentativelyidentified as extending from amino acid position 1 through about aminoacid position 20 in the sequence of FIG. 68 (SEQ ID NO:117).

[0679] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 123, inclusive of FIG. 68 (SEQ ID NO:117), or (b) thecomplement of the DNA of (a).

[0680] Another embodiment is directed to fragments of a PRO619polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 40 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[0681] In another embodiment, the invention provides isolated PRO619polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0682] In a specific aspect, the invention provides isolated nativesequence PRO619 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 21 through 123 of FIG. 68 (SEQ IDNO:117).

[0683] In another aspect, the invention concerns an isolated PRO619polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 through about 123, inclusive of FIG. 68 (SEQ ID NO:117).

[0684] In a further aspect, the invention concerns an isolated PRO619polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 123 of FIG. 68 (SEQ ID NO:117).

[0685] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO619 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 123,inclusive of FIG. 68 (SEQ ID NO:117), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0686] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO619 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO619 antibody.

[0687] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO619 polypeptide, bycontacting the native PRO619 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0688] In a still further embodiment, the invention concerns acomposition comprising a PRO619 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0689] 26. PRO943

[0690] A cDNA clone (DNA52192-1369) has been identified, having homologyto nucleic acid encoding fibroblast growth factor receptor-4 thatencodes a novel polypeptide, designated in the present application as“PRO943”.

[0691] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO943 polypeptide.

[0692] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO943 polypeptide having the sequence of amino acidresidues from about 1 or about 18 to about 504, inclusive of FIG. 70(SEQ ID NO:119), or (b) the complement of the DNA molecule of (a).

[0693] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO943 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 150 orabout 201 and about 1661, inclusive, of FIG. 69 (SEQ ID NO:118).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0694] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203042 (DNA52192-1369) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203042 (DNA52192-1369).

[0695] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 18 to about 504, inclusive of FIG. 70(SEQ ID NO:119), or (b) the complement of the DNA of (a).

[0696] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO943 polypeptide having the sequence of amino acid residuesfrom 1 or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[0697] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO943 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 17 in thesequence of FIG. 70 (SEQ ID NO:119). The transmembrane domain has beententatively identified as extending from about amino acid position 376to about amino acid position 396 in the PRO943 amino acid sequence (FIG.70, SEQ ID NO:119).

[0698] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119), or (b)the complement of the DNA of (a).

[0699] Another embodiment is directed to fragments of a PRO943polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 69 (SEQ ID NO:118).

[0700] In another embodiment, the invention provides isolated PRO943polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0701] In a specific aspect, the invention provides isolated nativesequence PRO943 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 18 to about 504 ofFIG. 70 (SEQ ID NO:119).

[0702] In another aspect, the invention concerns an isolated PRO943polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119).

[0703] In a further aspect, the invention concerns an isolated PRO943polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119).

[0704] In yet another aspect, the invention concerns an isolated PRO943polypeptide, comprising the sequence of amino acid residues 1 or about18 to about 504, inclusive of FIG. 70 (SEQ ID NO:119), or a fragmentthereof sufficient to provide a binding site for an anti-PRO943antibody. Preferably, the PRO943 fragment retains a qualitativebiological activity of a native PRO943 polypeptide.

[0705] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO943 polypeptide havingthe sequence of amino acid residues from about 1 or about 18 to about504, inclusive of FIG. 70 (SEQ ID NO:119), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0706] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO943 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO943 antibody.

[0707] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO943 polypeptide bycontacting the native PRO943 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0708] In a still further embodiment, the invention concerns acomposition comprising a PRO943 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0709] 27. PRO1188

[0710] A cDNA clone (DNA52598-1518) has been identified that encodes anovel polypeptide having homology to nucleotide pyrophosphohydrolase anddesignated in the present application as “PRO1188.”

[0711] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1188 polypeptide.

[0712] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1188 polypeptide having the sequence of aminoacid residues from about 22 to about 1184, inclusive of FIG. 72 (SEQ IDNO:124), or (b) the complement of the DNA molecule of (a).

[0713] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1188 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 199 andabout 3687, inclusive, of FIG. 71 (SEQ ID NO:123). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0714] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203107 (DNA52598-1518), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203107 (DNA52598-1518).

[0715] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 22 to about 1184, inclusive of FIG. 72(SEQ ID NO:124), or the complement of the DNA of (a).

[0716] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1188 polypeptide having the sequence of amino acid residues fromabout 22 to about 1184, inclusive of FIG. 72 (SEQ ID NO:124), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0717] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1188 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 21 in the sequence of FIG.72 (SEQ ID NO:124).

[0718] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 1184, inclusive of FIG. 72 (SEQ ID NO:124), or (b) thecomplement of the DNA of (a).

[0719] In another embodiment, the invention provides isolated PRO1188polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0720] In a specific aspect, the invention provides isolated nativesequence PRO1188 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 22 to 1184 of FIG. 72 (SEQ ID NO:124).

[0721] In another aspect, the invention concerns an isolated PRO1188polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 1184, inclusive of FIG. 72 (SEQ ID NO:124).

[0722] In a further aspect, the invention concerns an isolated PRO1188polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22 to1184 of FIG. 72 (SEQ ID NO:124).

[0723] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1188 polypeptide havingthe sequence of amino acid residues from about 22 to about 1184,inclusive of FIG. 72 (SEQ ID NO:124), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0724] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1188 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1188 antibody.

[0725] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1188 polypeptide, bycontacting the native PRO1188 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0726] In a still further embodiment, the invention concerns acomposition comprising a PRO1188 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier. 28. PRO1133

[0727] A cDNA clone (DNA53913-1490) has been identified that encodes anovel polypeptide having sequence identity with netrin-1a and designatedin the present application as “PRO1133.”

[0728] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1133 polypeptide.

[0729] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1133 polypeptide having the sequence of aminoacid residues from about 19 to about 438, inclusive of FIG. 74 (SEQ IDNO:129), or (b) the complement of the DNA molecule of (a).

[0730] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1133 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 320 andabout 1579, inclusive, of FIG. 73 (SEQ ID NO:128). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0731] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203162 (DNA53913-1490), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203162 (DNA53913-1490).

[0732] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 19 to about 438, inclusive of FIG. 74(SEQ ID NO:129), or the complement of the DNA of (a).

[0733] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1133 polypeptide having the sequence of amino acid residues fromabout 19 to about 438, inclusive of FIG. 74 (SEQ ID NO:129), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0734] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 438, inclusive of FIG. 74 (SEQ ID NO:129), or (b) thecomplement of the DNA of (a).

[0735] Another embodiment is directed to fragments of a PRO1133polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0736] In another embodiment, the invention provides isolated PRO1133polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0737] In a specific aspect, the invention provides isolated nativesequence PRO1133 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 19 through 438 of FIG. 74 (SEQ IDNO:129).

[0738] In another aspect, the invention concerns an isolated PRO1133polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 438, inclusive of FIG. 74 (SEQ ID NO:129).

[0739] In a further aspect, the invention concerns an isolated PRO1133polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19through 438 of FIG. 74 (SEQ ID NO:129).

[0740] In yet another aspect, the invention concerns an isolated PRO1133polypeptide, comprising the sequence of amino acid residues 19 to about438, inclusive of FIG. 74 (SEQ ID NO:129), or a fragment thereofsufficient to provide a binding site for an anti-PRO1133 antibody.Preferably, the PRO1133 fragment retains a qualitative biologicalactivity of a native PRO1133 polypeptide.

[0741] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1133 polypeptide havingthe sequence of amino acid residues from about 19 to about 438,inclusive of FIG. 74 (SEQ ID NO:129), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0742] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1133 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1133 antibody.

[0743] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1133 polypeptide, bycontacting the native PRO1133 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0744] In a still further embodiment, the invention concerns acomposition comprising a PRO1133 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0745] 29. PRO784

[0746] A cDNA clone (DNA53978-1443) has been identified that encodes anovel polypeptide, designated in the present application as “PRO784”.

[0747] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO784 polypeptide.

[0748] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO784 polypeptide having the sequence of amino acidresidues from about 16 to about 228, inclusive of FIG. 76 (SEQ IDNO:135), or (b) the complement of the DNA molecule of (a).

[0749] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO784 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 182 andabout 820, inclusive, of FIG. 75 (SEQ ID NO:134). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0750] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209983 (DNA53978-1443), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209983 (DNA53978-1443).

[0751] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 16 to about 228, inclusive of FIG. 76(SEQ ID NO:135), or the complement of the DNA of (a).

[0752] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 50, and preferably at least 100nucleotides and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO784polypeptide having the sequence of amino acid residues from about 16 toabout 228, inclusive of FIG. 76 (SEQ ID NO:135), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[0753] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO784 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position about 1 to about amino acid position 15 in thesequence of FIG. 76 (SEQ ID NO:135). The first transmembrane domain hasbeen tentatively identified as extending from about amino acid position68 to about amino acid position 87 in the PRO784 amino acid sequence(FIG. 76, SEQ ID NO:135).

[0754] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 16to about 228, inclusive of FIG. 76 (SEQ ID NO:135), or (b) thecomplement of the DNA of (a).

[0755] In another aspect, the invention concerns hybridization probesthat comprise fragments of the PRO784 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 40 to about 80 nucleotides.

[0756] In another embodiment, the invention provides isolated PRO784polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0757] In a specific aspect, the invention provides isolated nativesequence PRO784 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 16 to 228 of FIG. 76 (SEQ ID NO:135).

[0758] In another aspect, the invention concerns an isolated PRO784polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues16 to about 228, inclusive of FIG. 76 (SEQ ID NO:135).

[0759] In a further aspect, the invention concerns an isolated PRO784polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 16 to228 of FIG. 76 (SEQ ID NO:135).

[0760] In yet another aspect, the invention concerns an isolated PRO784polypeptide, comprising the sequence of amino acid residues 16 to about228, inclusive of FIG. 76 (SEQ ID NO:135), or a fragment thereofsufficient to provide a binding site for an anti-PRO784 antibody.Preferably, the PRO784 fragment retains a qualitative biologicalactivity of a native PRO784 polypeptide.

[0761] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO784 polypeptide havingthe sequence of amino acid residues from about 16 to about 228,inclusive of FIG. 76 (SEQ ID NO:135), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0762] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO784 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO784 antibody.

[0763] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO784 polypeptide, bycontacting the native PRO784 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0764] In a still further embodiment, the invention concerns acomposition comprising a PRO784 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0765] 30. PRO783

[0766] Applicants have identified a cDNA clone that encodes a novelmulti-span transmembrane polypeptide, wherein the polypeptide isdesignated in the present application as “PRO783”.

[0767] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO783 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO783polypeptide having amino acid residues 1 to 489 of FIG. 79 (SEQ IDNO:138), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO783 polypeptide having amino acidresidues 1 to X of FIG. 79 (SEQ ID NO:138), where X is any amino acidfrom 19 to 28 of FIG. 79 (SEQ ID NO:138), or is complementary to suchencoding nucleic acid sequence, and remains stably bound to it under atleast moderate, and optionally, under high stringency conditions. Theisolated nucleic acid sequence may comprise the cDNA insert of theDNA53996-1442 vector deposited on Jun. 2, 1998 as ATCC 209921 whichincludes the nucleotide sequence encoding PRO783.

[0768] In another embodiment, the invention provides isolated PRO783polypeptide. In particular, the invention provides isolated nativesequence PRO783 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 489 of FIG. 79 (SEQ ID NO:138).Additional embodiments of the present invention are directed to PRO783polypeptides comprising amino acid 1 to about X of FIG. 79 (SEQ IDNO:138), where X is any amino acid from 19 to 28 of FIG. 79 (SEQ IDNO:138). Optionally, the PRO783 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA53996-1442 vector deposited on Jun. 2, 1998, as ATCC 209921.

[0769] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA45201 which comprises thenucleic acid sequence shown in FIG. 80 (SEQ ID NO:139).

[0770] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA14575 which comprises thenucleic acid sequence shown in FIG. 81 (SEQ ID NO:140).

[0771] 31. PRO820

[0772] A cDNA clone (DNA56041-1416) has been identified, having sequenceidentity with immunoglobulin gamma Fe receptors that encodes a novelpolypeptide, designated in the present application as “PRO820”.

[0773] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO820 polypeptide.

[0774] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO820 polypeptide having the sequence of amino acidresidues from about 1 or 16 to about 124, inclusive of FIG. 83 (SEQ IDNO:146), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-124, or in anotherembodiment, 16-124.

[0775] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO820 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 115 or 160and about 486, inclusive, of FIG. 82 (SEQ ID NO:145). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0776] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203021 (DNA56041-1416), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. (DNA56041-1416).

[0777] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 16 to about 124, inclusive of FIG.83 (SEQ ID NO:146), or the complement of the DNA of (a).

[0778] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO820polypeptide having the sequence of amino acid residues from about 1 or16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0779] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146), or (b) thecomplement of the DNA of (a).

[0780] In another embodiment, the invention provides isolated PRO820polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0781] In a specific aspect, the invention provides isolated nativesequence PRO820 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 16 through 124 of FIG. 83 (SEQ IDNO:146).

[0782] In another aspect, the invention concerns an isolated PRO820polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 16 to about 124, inclusive of FIG. 83 (SEQ ID NO:146).

[0783] In a further aspect, the invention concerns an isolated PRO820polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 16through 124 of FIG. 83 (SEQ ID NO:146).

[0784] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO820 polypeptide havingthe sequence of amino acid residues from about 1 or 16 to about 124,inclusive of FIG. 83 (SEQ ID NO:146), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0785] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO820 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO820 antibody.

[0786] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO820 polypeptide, bycontacting the native PRO820 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0787] In a still further embodiment, the invention concerns acomposition comprising a PRO820 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[0788] 32. PRO1080

[0789] A cDNA clone (DNA56047-1456) has been identified that encodes anovel polypeptide, designated in the present application as “PRO108O.”PRO1080 polypeptides have sequence identity with DnaJ proteins.

[0790] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1080 polypeptide.

[0791] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1080 polypeptide having the sequence of aminoacid residues from about 1 or 23 to about 358, inclusive of FIG. 85 (SEQID NO:148), or (b) the complement of the DNA molecule of (a). The term“or” as used herein to refer to amino or nucleic acids is meant to referto two alternative embodiments provided herein, i.e., 1-358, or inanother embodiment, 23-358.

[0792] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1080 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 159 or 225and about 1232, inclusive, of FIG. 84 (SEQ ID NO:147). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0793] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209948 (DNA56047-1456), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209948 (DNA56047-1456).

[0794] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 23 to about 358, inclusive of FIG.85 (SEQ ID NO:148), or the complement of the DNA of (a).

[0795] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1080polypeptide having the sequence of amino acid residues from about 1 or23 to about 358, inclusive of FIG. 85 (SEQ ID NO:148), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0796] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1080 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 22 in thesequence of FIG. 85 (SEQ ID NO:148).

[0797] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 23 to about 358, inclusive of FIG. 85 (SEQ ID NO:148), or (b) thecomplement of the DNA of (a).

[0798] In another embodiment, the invention provides isolated PRO1080polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0799] In a specific aspect, the invention provides isolated nativesequence PRO1080 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 23 through 358 of FIG. 85 (SEQ IDNO:148).

[0800] In another aspect, the invention concerns an isolated PRO1080polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 23 to about 358, inclusive of FIG. 85 (SEQ ID NO:148).

[0801] In a further aspect, the invention concerns an isolated PRO1080polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 23through 358 of FIG. 85 (SEQ ID NO:148).

[0802] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1080 polypeptide havingthe sequence of amino acid residues from about 1 or 23 to about 358,inclusive of FIG. 85 (SEQ ID NO:148), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0803] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1080 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1080 antibody.

[0804] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1080 polypeptide, bycontacting the native PRO1080 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0805] In a still further embodiment, the invention concerns acomposition comprising a PRO1080 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0806] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA36527 comprising thenucleotide sequence of FIG. 86 (SEQ ID NO:149).

[0807] 33. PRO1079

[0808] A cDNA clone (DNA56050-1455) has been identified that encodes anovel polypeptide, designated in the present application as “PRO1079”.

[0809] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1079 polypeptide.

[0810] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1079 polypeptide having the sequence of aminoacid residues from about 30 to about 226, inclusive of FIG. 88 (SEQ IDNO:151), or (b) the complement of the DNA molecule of (a).

[0811] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1079 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 270 andabout 860, inclusive, of FIG. 87 (SEQ ID NO:150). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0812] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203011 (DNA56050-1455), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203011 (DNA56050-1455).

[0813] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 30 to about 226, inclusive of FIG. 88(SEQ ID NO:151), or the complement of the DNA of (a).

[0814] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides and preferably atleast about 100 nucleotides, and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1079 polypeptide having the sequence of amino acid residues fromabout 30 to about 226, inclusive of FIG. 88 (SEQ ID NO:151), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0815] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1079 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 29 in thesequence of FIG. 88 (SEQ ID NO:151).

[0816] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 30to about 226, inclusive of FIG. 88 (SEQ ID NO:151), or (b) thecomplement of the DNA of (a).

[0817] Another embodiment is directed to fragments of a PRO1079polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0818] In another embodiment, the invention provides isolated PRO1079polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0819] In a specific aspect, the invention provides isolated nativesequence PRO1079 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 30 to 226 of FIG. 88 (SEQ ID NO:151).

[0820] In another aspect, the invention concerns an isolated PRO1079polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues30 to about 226, inclusive of FIG. 88 (SEQ ID NO:151).

[0821] In a further aspect, the invention concerns an isolatedPRO1079polypeptide, comprising an amino acid sequence scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 30to 226 of FIG. 88 (SEQ ID NO:151).

[0822] In yet another aspect, the invention concerns an isolated PRO1079polypeptide, comprising the sequence of amino acid residues 30 to about226, inclusive of FIG. 88 (SEQ ID NO:151), or a fragment thereofsufficient to provide a binding site for an anti-PRO1079 antibody.Preferably, the PRO1079 fragment retains a qualitative biologicalactivity of a native PRO1079 polypeptide.

[0823] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1079 polypeptide havingthe sequence of amino acid residues from about 30 to about 226,inclusive of FIG. 88 (SEQ ID NO:151), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0824] 34. PRO793

[0825] A cDNA clone (DNA56110-1437) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO793”.

[0826] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO793 polypeptide.

[0827] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO793 polypeptide having the sequence of amino acidresidues from about 1 to about 138, inclusive of FIG. 90 (SEQ IDNO:153), or (b) the complement of the DNA molecule of (a).

[0828] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO793 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 77 andabout 490, inclusive, of FIG. 89 (SEQ ID NO:152). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0829] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203113 (DNA56110-1437) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203113 (DNA56110-1437).

[0830] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 to about 138, inclusive of FIG. 90 (SEQ IDNO:153), or (b) the complement of the DNA of (a).

[0831] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO793 polypeptide having the sequence of amino acid residuesfrom 1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, prefereably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0832] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO793 polypeptide, with orwithout the initiating methionine, and its soluble, i.e., transmembranedomain deleted or inactivated variants, or is complementary to suchencoding nucleic acid molecule. The transmembrane domains have beententatively identified as extending from about amino acid position 12 toabout amino acid position 30, from about amino acid position 33 to aboutamino acid position 52, from about amino acid position 69 to about aminoacid position 89 and from about amino acid position 93 to about aminoacid position 109 in the PRO793 amino acid sequence (FIG. 90, SEQ IDNO:153).

[0833] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 138, inclusive of FIG. 90 (SEQ ID NO:153), or (b) thecomplement of the DNA of (a).

[0834] Another embodiment is directed to fragments of a PRO793polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 89 (SEQ ID NO:152).

[0835] In another embodiment, the invention provides isolated PRO793polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0836] In a specific aspect, the invention provides isolated nativesequence PRO793 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 to about 138 of FIG. 90 (SEQID NO:153).

[0837] In another aspect, the invention concerns an isolated PRO793polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 138, inclusive of FIG. 90 (SEQ ID NO:153).

[0838] In a further aspect, the invention concerns an isolated PRO793polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 138, inclusive of FIG. 90 (SEQ ID NO:153).

[0839] In yet another aspect, the invention concerns an isolated PRO793polypeptide, comprising the sequence of amino acid residues 1 to about138, inclusive of FIG. 90 (SEQ ID NO:153), or a fragment thereofsufficient to provide a binding site for an anti-PRO793 antibody.Preferably, the PRO793 fragment retains a qualitative biologicalactivity of a native PRO793 polypeptide.

[0840] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO793 polypeptide havingthe sequence of amino acid residues from about 1 to about 138, inclusiveof FIG. 90 (SEQ ID NO:153), or (b) the complement of the DNA molecule of(a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0841] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA50177 comprising thenucleotide sequence of FIG. 91 (SEQ ID NO:154).

[0842] 35. PRO1016

[0843] A cDNA clone (DNA56113-1378) has been identified, having sequenceidentity with acyltransferases that encodes a novel polypeptide,designated in the present application as “PRO1016”.

[0844] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1016 polypeptide.

[0845] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1016 polypeptide having the sequence of aminoacid residues from about 1 or 19 to about 378, inclusive of FIG. 93 (SEQID NO:156), or (b) the complement of the DNA molecule of (a). The term“or” as used herein to refer to amino or nucleic acids is meant to referto two alternative embodiments provided herein, i.e., 1-378, or inanother embodiment, 19-378.

[0846] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1016 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 168 or 222and about 1301, inclusive, of FIG. 92 (SEQ ID NO:155). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0847] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203049 (DNA56113-1378), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203049 (DNA56113-1378).

[0848] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 19 to about 378, inclusive of FIG.93 (SEQ ID NO:156), or the complement of the DNA of (a).

[0849] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1016polypeptide having the sequence of amino acid residues from about 1 or19 to about 378, inclusive of FIG. 93 (SEQ ID NO:156), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0850] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1016 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domains deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 18 in thesequence of FIG. 93 (SEQ ID NO:156). The transmembrane domains have beententatively identified as extending from about amino acid position 305through about amino acid position 330 and from about amino acid position332 through about amino acid position 352 in the PRO1016 amino acidsequence (FIG. 93, SEQ ID NO:156).

[0851] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 378, inclusive of FIG. 93 (SEQ ID NO:156), or (b) thecomplement of the DNA of (a).

[0852] In another embodiment, the invention provides isolated PRO1016polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0853] In a specific aspect, the invention provides isolated nativesequence PRO1016 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 19 through 378 of FIG. 93 (SEQ IDNO:156).

[0854] In another aspect, the invention concerns an isolated PRO1016polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 378, inclusive of FIG. 93 (SEQ ID NO:156).

[0855] In a further aspect, the invention concerns an isolated PRO1016polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 378 of FIG. 93 (SEQ ID NO:156).

[0856] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1016 polypeptide havingthe sequence of amino acid residues from about 1 or 19 to about 378,inclusive of FIG. 93 (SEQ ID NO:156), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0857] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1016 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1016 antibody.

[0858] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1016 polypeptide, bycontacting the native PRO1016 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0859] In a still further embodiment, the invention concerns acomposition comprising a PRO1016 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0860] 36. PRO1013

[0861] Applicants have identified a cDNA clone that encodes a novelpolypeptide having sequence identity with P120, wherein the polypeptideis designated in the present application as “PRO1013”.

[0862] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1013 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1013polypeptide having amino acid residues 1 through 409 of FIG. 95 (SEQ IDNO:158), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. The isolated nucleic acid sequence maycomprise the cDNA insert of the vector deposited on Jun. 2, 1998 withthe ATCC as DNA56410-1414 which includes the nucleotide sequenceencoding PRO1013.

[0863] In another embodiment, the invention provides isolated PRO1013polypeptide. In particular, the invention provides isolated nativesequence PRO1013 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 409 of FIG. 95 (SEQ IDNO:158). Optionally, the PRO1013 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe vector deposited on Jun. 2, 1998 with the ATCC as DNA56410-1414. 37.PRO937

[0864] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to glypican family proteins, wherein thepolypeptide is designated in the present application as “PRO937”.

[0865] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO937 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO937polypeptide having amino acid residues 1 to 556 of FIG. 97 (SEQ IDNO:160), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO937 polypeptide having amino acidresidues about 23 to 556 of FIG. 97 (SEQ ID NO:160), or is complementaryto such encoding nucleic acid sequence, and remains stably bound to itunder at least moderate, and optionally, under high stringencyconditions. The isolated nucleic acid sequence may comprise the cDNAinsert of the DNA56436-1448 vector deposited on May 27, 1998, as ATCC209902 which includes the nucleotide sequence encoding PRO937.

[0866] In another embodiment, the invention provides isolated PRO937polypeptide. In particular, the invention provides isolated nativesequence PRO937 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 556 of FIG. 97 (SEQ ID NO:160).Additional embodiments of the present invention are directed to PRO937polypeptides comprising amino acids about 23 to 556 of FIG. 97 (SEQ IDNO:160). Optionally, the PRO937 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA56436-1448 vector deposited on May 27, 1998 as ATCC 209902.

[0867] 38. PRO842

[0868] A cDNA clone (DNA56855-1447) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO842.” In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO842 polypeptide.

[0869] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO842 polypeptide having the sequence of amino acidresidues from about 23 to about 119, inclusive of FIG. 99 (SEQ IDNO:165), or (b) the complement of the DNA molecule of (a).

[0870] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO842 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 219 andabout 509, inclusive, of FIG. 98 (SEQ ID NO:164). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0871] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203004 (DNA56855-1447), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203004 (DNA56855-1447).

[0872] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 23 to about 119, inclusive of FIG. 99(SEQ ID NO:165), or the complement of the DNA of (a).

[0873] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides, and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO842 polypeptide having the sequence of amino acid residues from about23 to about 119, inclusive of FIG. 99 (SEQ ID NO:165), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0874] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO842 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 22 in thesequence of FIG. 99 (SEQ ID NO:165).

[0875] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 119, inclusive of FIG. 99 (SEQ ID NO:165), or (b) thecomplement of the DNA of (a).

[0876] Another embodiment is directed to fragments of a PRO842polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0877] In another embodiment, the invention provides isolated PRO842polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0878] In a specific aspect, the invention provides isolated nativesequence PRO842 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 23 to 119 of FIG. 99 (SEQ ID NO:165).

[0879] In another aspect, the invention concerns an isolated PRO842polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 119, inclusive of FIG. 99 (SEQ ID NO:165).

[0880] In a further aspect, the invention concerns an isolated PRO842polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23 to119 of FIG. 99 (SEQ ID NO:165).

[0881] In yet another aspect, the invention concerns an isolated PRO842polypeptide, comprising the sequence of amino acid residues 23 to about119, inclusive of FIG. 99 (SEQ ID NO:165), or a fragment thereofsufficient to provide a binding site for an anti-PRO842 antibody.Preferably, the PRO842 fragment retains a qualitative biologicalactivity of a native PRO842 polypeptide.

[0882] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO842 polypeptide havingthe sequence of amino acid residues from about 23 to about 119,inclusive of FIG. 99 (SEQ ID NO:165), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0883] 39. PRO839

[0884] A cDNA clone (DNA56859-1445) has been identified that encodes anovel polypeptide, designated in the present application as “PRO839.”

[0885] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO839 polypeptide.

[0886] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO839 polypeptide having the sequence of amino acidresidues from about 24 to about 87, inclusive of FIG. 101 (SEQ IDNO:167), or (b) the complement of the DNA molecule of (a).

[0887] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO839 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 71 andabout 262, inclusive, of FIG. 100 (SEQ ID NO:166). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0888] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203019 (DNA56859-1445), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203019 (DNA56859-1445).

[0889] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 24 to about 87, inclusive of FIG. 101(SEQ ID NO:167), or the complement of the DNA of (a).

[0890] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 50 nucleotides, and preferably at least100 nucleotides and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO839polypeptide having the sequence of amino acid residues from about 24 toabout 87, inclusive of FIG. 101 (SEQ ID NO:167), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[0891] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO839 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 23 in thesequence of FIG. 101 (SEQ ID NO:167).

[0892] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 24to about 87, inclusive of FIG. 101 (SEQ ID NO:167), or (b) thecomplement of the DNA of (a).

[0893] Another embodiment is directed to fragments of a PRO839polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0894] In another embodiment, the invention provides isolated PRO839polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0895] In a specific aspect, the invention provides isolated nativesequence PRO839 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 24 to 87 of FIG. 101 (SEQ ID NO:167).

[0896] In another aspect, the invention concerns an isolated PRO839polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues24 to about 87, inclusive of FIG. 101 (SEQ ID NO:167).

[0897] In a further aspect, the invention concerns an isolated PRO839polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 24 to87 of FIG. 101 (SEQ ID NO:167).

[0898] In yet another aspect, the invention concerns an isolated PRO839polypeptide, comprising the sequence of amino acid residues 24 to about87, inclusive of FIG. 101 (SEQ ID NO:167), or a fragment thereofsufficient to provide a binding site for an anti-PRO839 antibody.Preferably, the PRO839 fragment retains a qualitative biologicalactivity of a native PRO839 polypeptide.

[0899] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO839 polypeptide havingthe sequence of amino acid residues from about 24 to about 87, inclusiveof FIG. 101 (SEQ ID NO:167), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0900] 40. PRO1180

[0901] Applicants have identified a cDNA clone (DNA56860-1510) havinghomology to nucleic acid encoding methyltransferase enzymes that encodesa novel polypeptide, designated in the present application as “PRO1180”.

[0902] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1180 polypeptide.

[0903] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1180 polypeptide having the sequence of aminoacid residues from about 1 or about 24 to about 277, inclusive of FIG.103 (SEQ ID NO:169), or (b) the complement of the DNA molecule of (a).

[0904] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1180 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 78 orabout 147 and about 908, inclusive of FIG. 102 (SEQ ID NO:168).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0905] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209952 (DNA56860-1510). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209952(DNA56860-1510).

[0906] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 24 to about 277, inclusive of FIG. 103(SEQ ID NO:169).

[0907] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1180 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 23 in the sequence of FIG.103 (SEQ ID NO:169).

[0908] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

[0909] Another embodiment is directed to fragments of a PRO1180polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[0910] In another embodiment, the invention provides isolated PRO1180polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0911] In a specific aspect, the invention provides isolated nativesequence PRO1180 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 24 to about 277 of FIG. 103(SEQ ID NO:169).

[0912] In another aspect, the invention concerns an isolated PRO1180polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

[0913] In a further aspect, the invention concerns an isolated PRO1180polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169).

[0914] In yet another aspect, the invention concerns an isolated PRO1180polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 277, inclusive of FIG. 103 (SEQ ID NO:169), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1180antibody. Preferably, the PRO1180 fragment retains a qualitativebiological activity of a native PRO1180 polypeptide.

[0915] In another aspect, the present invention is directed to fragmentsof a PRO1180 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[0916] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1180 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1180 antibody.

[0917] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1180 polypeptide.

[0918] In still a further embodiment, the invention concerns acomposition comprising a PRO1180 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0919] 41. PRO1134

[0920] A cDNA clone (DNA56865-1491) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1134”.

[0921] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1134 polypeptide.

[0922] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1134 polypeptide having the sequence of aminoacid residues from about 1 or about 24 to about 371, inclusive of FIG.105 (SEQ ID NO:171), or (b) the complement of the DNA molecule of (a).

[0923] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1134 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 153 orabout 222 and about 1265, inclusive, of FIG. 104 (SEQ ID NO:170).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0924] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203022 (DNA56865-1491) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203022 (DNA56865-1491).

[0925] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 24 to about 371, inclusive of FIG. 105(SEQ ID NO:171), or (b) the complement of the DNA of (a).

[0926] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1134 polypeptide having the sequence of amino acidresidues from 1 or about 24 to about 371, inclusive of FIG. 105 (SEQ IDNO:171), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[0927] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1134 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 23 in the sequence of FIG.105 (SEQ ID NO:171).

[0928] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171), or (b)the complement of the DNA of (a).

[0929] Another embodiment is directed to fragments of a PRO1134polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 104 (SEQ ID NO:170).

[0930] In another embodiment, the invention provides isolated PRO1134polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0931] In a specific aspect, the invention provides isolated nativesequence PRO1134 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 24 to about 371 ofFIG. 105 (SEQ ID NO:171).

[0932] In another aspect, the invention concerns an isolated PRO1134polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171).

[0933] In a further aspect, the invention concerns an isolated PRO1134polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171).

[0934] In yet another aspect, the invention concerns an isolated PRO1134polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 371, inclusive of FIG. 105 (SEQ ID NO:171), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1134antibody. Preferably, the PRO1134 fragment retains a qualitativebiological activity of a native PRO1134 polypeptide.

[0935] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1134 polypeptide havingthe sequence of amino acid residues from about 1 or about 24 to about371, inclusive of FIG. 105 (SEQ ID NO:171), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0936] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA52352 comprising thenucleotide sequence of SEQ ID NO:172 (see FIG. 106).

[0937] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA55725 comprising thenucleotide sequence of SEQ ID NO:173 (see FIG. 107).

[0938] 42. PRO830

[0939] A cDNA clone (DNA56866-1342) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO830”.

[0940] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO830 polypeptide.

[0941] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO830 polypeptide having the sequence of amino acidresidues from about 1 or about 34 to about 87, inclusive of FIG. 109(SEQ ID NO:175), or (b) the complement of the DNA molecule of (a).

[0942] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO830 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 154 orabout 253 and about 414, inclusive, of FIG. 108 (SEQ ID NO:174).Preferably, hybridization occurs under stringent hybridization and washconditions.

[0943] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203023 (DNA56866-1342) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203023 (DNA56866-1342).

[0944] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 34 to about 87, inclusive of FIG. 109(SEQ ID NO:175), or (b) the complement of the DNA of (a).

[0945] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO830 polypeptide having the sequence of amino acid residuesfrom 1 or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[0946] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO830 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 33 in the sequence of FIG.109 (SEQ ID NO:175).

[0947] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175), or (b)the complement of the DNA of (a).

[0948] Another embodiment is directed to fragments of a PRO830polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 108 (SEQ ID NO:174).

[0949] In another embodiment, the invention provides isolated PRO830polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[0950] In a specific aspect, the invention provides isolated nativesequence PRO830 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 34 to about 87 ofFIG. 109 (SEQ ID NO:175).

[0951] In another aspect, the invention concerns an isolated PRO830polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175).

[0952] In a further aspect, the invention concerns an isolated PRO830polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175).

[0953] In yet another aspect, the invention concerns an isolated PRO830polypeptide, comprising the sequence of amino acid residues 1 or about34 to about 87, inclusive of FIG. 109 (SEQ ID NO:175), or a fragmentthereof sufficient to provide a binding site for an anti-PRO830antibody. Preferably, the PRO830 fragment retains a qualitativebiological activity of a native PRO830 polypeptide.

[0954] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO830 polypeptide havingthe sequence of amino acid residues from about 1 or about 34 to about87, inclusive of FIG. 109 (SEQ ID NO:175), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[0955] 43. PRO1115

[0956] A cDNA clone (DNA56868-1478) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO1115”.

[0957] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1115 polypeptide.

[0958] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1115 polypeptide having the sequence of aminoacid residues from about 21 to about 445, inclusive of FIG. 111 (SEQ IDNO:177), or (b) the complement of the DNA molecule of (a).

[0959] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1115 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 249 andabout 1523, inclusive, of FIG. 110 (SEQ ID NO:176). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0960] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203024 (DNA56868-1478), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203024 (DNA56868-1478).

[0961] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 21 to about 445, inclusive of FIG. 111(SEQ ID NO:177), or the complement of the DNA of (a).

[0962] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1115 polypeptide having the sequence of amino acid residues fromabout 21 to about 445, inclusive of FIG. 111 (SEQ ID NO:177), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0963] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1115 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and one or more of its transmembrane domains deleted or inactivated, oris complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 20 in the sequence of FIG.111 (SEQ ID NO:177). Transmembrane domains have been tentativelyidentified as extending from about amino acid positions 35-54, 75-97,126-146, 185-204, 333-350, and 352-371 in the PRO1115 amino acidsequence (FIG. 111, SEQ ID NO:177).

[0964] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 445, inclusive of FIG. 111 (SEQ ID NO:177), or (b) thecomplement of the DNA of (a).

[0965] Another embodiment is directed to fragments of a PRO1115polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0966] In another embodiment, the invention provides isolated PRO115polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0967] In a specific aspect, the invention provides isolated nativesequence PRO115 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 21 to 445 of FIG. 111 (SEQ ID NO:177).

[0968] In another aspect, the invention concerns an isolated PRO1115polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 445, inclusive of FIG. 111 (SEQ ID NO:177).

[0969] In a further aspect, the invention concerns an isolated PRO1115polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to445 of FIG. 111 (SEQ ID NO:177).

[0970] In yet another aspect, the invention concerns an isolated PRO1115polypeptide, comprising the sequence of amino acid residues 21 to about445, inclusive of FIG. 111 (SEQ ID NO:177), or a fragment thereofsufficient to provide a binding site for an anti-PRO1115 antibody.Preferably, the PRO1115 fragment retains a qualitative biologicalactivity of a native PRO1115 polypeptide.

[0971] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1115 polypeptide havingthe sequence of amino acid residues from about 21 to about 445,inclusive of FIG. 111 (SEQ ID NO:177), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0972] 44. PRO1277

[0973] A cDNA clone (DNA56869-1545) has been identified that encodes anovel polypeptide having homology to Coch-5B2 and designated in thepresent application as “PRO1277.”

[0974] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1277 polypeptide.

[0975] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1277 polypeptide having the sequence of aminoacid residues from about 27 to about 678, inclusive of FIG. 113 (SEQ IDNO:179), or (b) the complement of the DNA molecule of (a).

[0976] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1277 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 266 andabout 2221, inclusive, of FIG. 112 (SEQ ID NO:178). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[0977] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203161 (DNA56869-1545), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203161 (DNA56869-1545).

[0978] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 27 to about 678, inclusive of FIG. 113(SEQ ID NO:179), or the complement of the DNA of (a).

[0979] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1277 polypeptide having the sequence of amino acid residues fromabout 27 to about 678, inclusive of FIG. 113 (SEQ ID NO:179), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[0980] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1277 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 26 in thesequence of FIG. 113 (SEQ ID NO:179). The transmembrane domain has beententatively identified as extending from about amino acid position 181to about amino acid position 200 in the PRO1277 amino acid sequence(FIG. 113, SEQ ID NO:179).

[0981] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 27to about 678, inclusive of FIG. 113 (SEQ ID NO:179), or (b) thecomplement of the DNA of (a).

[0982] Another embodiment is directed to fragments of a PRO1277polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[0983] In another embodiment, the invention provides isolated PRO1277polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[0984] In a specific aspect, the invention provides isolated nativesequence PRO1277 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 27 to 678 of FIG. 113 (SEQ ID NO:179).

[0985] In another aspect, the invention concerns an isolated PRO1277polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues27 to about 678, inclusive of FIG. 113 (SEQ ID NO:179).

[0986] In a further aspect, the invention concerns an isolated PRO1277polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 27 to678 of FIG. 113 (SEQ ID NO:179).

[0987] In yet another aspect, the invention concerns an isolated PRO1277polypeptide, comprising the sequence of amino acid residues 27 to about678, inclusive of FIG. 113 (SEQ ID NO:179), or a fragment thereofsufficient to provide a binding site for an anti-PRO1277 antibody.Preferably, the PRO1277 fragment retains a qualitative biologicalactivity of a native PRO1277 polypeptide.

[0988] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1277 polypeptide havingthe sequence of amino acid residues from about 27 to about 678,inclusive of FIG. 113 (SEQ ID NO:179), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[0989] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1277 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1277 antibody.

[0990] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1277 polypeptide, bycontacting the native PRO1277 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[0991] In a still further embodiment, the invention concerns acomposition comprising a PRO1277 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[0992] 45. PRO1135

[0993] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to alpha 1,2-mannosidase, wherein thepolypeptide is designated in the present application as “PRO1135”.

[0994] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1135 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1135polypeptide having amino acid residues 1 to 541 of FIG. 115 (SEQ IDNO:181), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO1135 polypeptide having amino acidresidues about 22 to 541 of FIG. 115 (SEQ ID NO:181), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA56870-1492 vector deposited on Jun. 2, 1998 asATCC 209925 which includes the nucleotide sequence encoding PRO1135.

[0995] In another embodiment, the invention provides isolated PRO1135polypeptide. In particular, the invention provides isolated nativesequence PRO1135 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 541 of FIG. 115 (SEQ ID NO:181).Additional embodiments of the present invention are directed to PRO1135polypeptides comprising amino acids about 22 to 541 of FIG. 115 (SEQ IDNO:181). Optionally, the PRO1135 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA56870-1492 vector deposited on Jun. 2, 1998 as ATCC 209925.

[0996] 46. PRO1114

[0997] A cDNA clone (DNA57033-1403) has been identified that encodes anovel interferon receptor polypeptide, designated in the presentapplication as “PRO1114 interferon receptor”.

[0998] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1114 interferon receptorpolypeptide.

[0999] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1114 interferon receptor polypeptide having thesequence of amino acid residues from about 1 or about 30 to about 311,inclusive of FIG. 117 (SEQ ID NO:183), or (b) the complement of the DNAmolecule of (a).

[1000] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1114 interferon receptor polypeptidecomprising DNA hybridizing to the complement of the nucleic acid betweenabout nucleotides 250 or about 337 and about 1182, inclusive, of FIG.116 (SEQ ID NO:182). Preferably, hybridization occurs under stringenthybridization and wash conditions.

[1001] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209905 (DNA57033-1403) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209905 (DNA57033-1403).

[1002] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 30 to about 311, inclusive of FIG. 117(SEQ ID NO:183), or (b) the complement of the DNA of (a).

[1003] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1114 interferon receptor polypeptide having the sequenceof amino acid residues from 1 or about 30 to about 311, inclusive ofFIG. 117 (SEQ ID NO:183), or (b) the complement of the DNA molecule of(a), and, if the DNA molecule has at least about an 80% sequenceidentity, prefereably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), isolating the testDNA molecule.

[1004] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO114 interferon receptorpolypeptide, with or without the N-terminal signal sequence and/or theinitiating methionine, and its soluble, i.e., transmembrane domaindeleted or inactivated variants, or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from about amino acid position 1 to about aminoacid position 29 in the sequence of FIG. 117 (SEQ ID NO:183). Thetransmembrane domain has been tentatively identified as extending fromabout amino acid position 230 to about amino acid position 255 in thePRO1114 interferon receptor amino acid sequence (FIG. 117, SEQ IDNO:183).

[1005] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 30 to about 311, inclusive of FIG. 117 (SEQ ID NO:183), or (b)the complement of the DNA of (a).

[1006] Another embodiment is directed to fragments of a PRO1114interferon receptor polypeptide coding sequence that may find use ashybridization probes. Such nucleic acid fragments are from about 20 toabout 80 nucleotides in length, preferably from about 20 to about 60nucleotides in length, more preferably from about 20 to about 50nucleotides in length and most preferably from about 20 to about 40nucleotides in length and may be derived from the nucleotide sequenceshown in FIG. 116 (SEQ ID NO:182).

[1007] In another embodiment, the invention provides isolated PRO1114interferon receptor polypeptide encoded by any of the isolated nucleicacid sequences hereinabove identified.

[1008] In a specific aspect, the invention provides isolated nativesequence PRO1114 interferon receptor polypeptide, which in certainembodiments, includes an amino acid sequence comprising residues 1 orabout 30 to about 311 of FIG. 117 (SEQ ID NO:183).

[1009] In another aspect, the invention concerns an isolated PRO1114interferon receptor polypeptide, comprising an amino acid sequencehaving at least about 80% sequence identity, preferably at least about85% sequence identity, more preferably at least about 90% sequenceidentity, most preferably at least about 95% sequence identity to thesequence of amino acid residues 1 or about 30 to about 311, inclusive ofFIG. 117 (SEQ ID NO:183).

[1010] In a further aspect, the invention concerns an isolated PRO1114interferon receptor polypeptide, comprising an amino acid sequencescoring at least about 80% positives, preferably at least about 85%positives, more preferably at least about 90% positives, most preferablyat least about 95% positives when compared with the amino acid sequenceof residues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183).

[1011] In yet another aspect, the invention concerns an isolated PRO1114interferon receptor polypeptide, comprising the sequence of amino acidresidues 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ IDNO:183), or a fragment thereof sufficient to provide a binding site foran anti-PRO114 interferon receptor antibody. Preferably, the PRO1114interferon receptor fragment retains a qualitative biological activityof a native PRO1114 interferon receptor polypeptide.

[1012] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1114 interferonreceptor polypeptide having the sequence of amino acid residues fromabout 1 or about 30 to about 311, inclusive of FIG. 117 (SEQ ID NO:183),or (b) the complement of the DNA molecule of (a), and if the test DNAmolecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), (ii) culturing a host cell comprising the testDNA molecule under conditions suitable for expression of thepolypeptide, and (iii) recovering the polypeptide from the cell culture.

[1013] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1114 -interferon receptor polypeptide. In aparticular embodiment, the agonist or antagonist is an anti-PRO1114interferon receptor antibody.

[1014] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1114 interferonreceptor polypeptide by contacting the native PRO1114 interferonreceptor polypeptide with a candidate molecule and monitoring abiological activity mediated by said polypeptide.

[1015] In a still further embodiment, the invention concerns acomposition comprising a PRO1114 interferon receptor polypeptide, or anagonist or antagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1016] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA48466 comprising thenucleotide sequence of SEQ ID NO:184 (see FIG. 118).

[1017] 47. PRO828

[1018] Applicants have identified a cDNA clone that encodes a novelpolypeptide having homology to glutathione peroxidases wherein thepolypeptide is designated in the present application as “PRO828”.

[1019] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO828 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO828polypeptide having amino acid residues 1 to 187 of FIG. 120 (SEQ IDNO:189), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO828 polypeptide having amino acidresidues about 22 to 187 of FIG. 120 (SEQ ID NO:189), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA57037-1444 vector deposited on May 27, 1998 asATCC 209903 which includes the nucleotide sequence encoding PRO828.

[1020] In another embodiment, the invention provides isolated PRO828polypeptide. In particular, the invention provides isolated nativesequence PRO828 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 187 of FIG. 120 (SEQ ID NO:189).Additional embodiments of the present invention are directed to PRO828polypeptides comprising amino acids about 22 to 187 of FIG. 120 (SEQ IDNO:189). Optionally, the PRO828 polypeptide is obtained or is obtainableby expressing the polypeptide encoded by the cDNA insert of theDNA57037-1444 vector deposited on May 27, 1998 as ATCC 209903.

[1021] 48. PRO1009

[1022] A cDNA clone (DNA57129-1413) has been identified, having sequenceidentity with a long chain acyl-CoA synthetase homologue, a long chainacyl-CoA synthetase and a long chain acyl-CoA synthetase ligase thatencodes a novel polypeptide, designated in the present application as“PRO1009.”

[1023] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1009 polypeptide.

[1024] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1009 polypeptide having the sequence of aminoacid residues from about 1 or 23 to about 615, inclusive of FIG. 122(SEQ ID NO:194), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to amino or nucleic acids is meant torefer to two separate alternative embodiments provided herein, i.e.,1-615 or 23-615.

[1025] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1009 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 41 or 107and about 1885, inclusive, of FIG. 121 (SEQ ID NO:193). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1026] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209977 (DNA57129-1413), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209977 (DNA57129-1413).

[1027] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 23 to about 615, inclusive of FIG.122 (SEQ ID NO:194), or the complement of the DNA of (a).

[1028] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1009polypeptide having the sequence of amino acid residues from about 1 or23 to about 615, inclusive of FIG. 122 (SEQ ID NO:194), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1029] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1009 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 to about amino acid position 22 in the sequence ofFIG. 122 (SEQ ID NO:194). The transmembrane domains have beententatively identified as extending from about amino acid positions140-161, 213-229 and 312-334 in the PRO1009 amino acid sequence (FIG.122, SEQ ID NO:194).

[1030] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 23 to about 615, inclusive of FIG. 122 (SEQ ID NO:194), or (b) thecomplement of the DNA of (a).

[1031] In another embodiment, the invention provides isolated PRO1009polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1032] In a specific aspect, the invention provides isolated nativesequence PRO1009 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 23 to 615 of FIG. 122 (SEQ IDNO:194).

[1033] In another aspect, the invention concerns an isolated PRO1009polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 23 to about 615, inclusive of FIG. 122 (SEQ ID NO:194).

[1034] In a further aspect, the invention concerns an isolated PRO1009polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 23to 615 of FIG. 122 (SEQ ID NO:194).

[1035] In yet another aspect, the invention concerns an isolated PRO1009polypeptide, comprising the sequence of amino acid residues 1 or 23 toabout 615, inclusive of FIG. 122 (SEQ ID NO:194), or a fragment thereofsufficient to provide a binding site for an anti-PRO1009 antibody.Preferably, the PRO1009 fragment retains a qualitative biologicalactivity of a native PRO1009 polypeptide.

[1036] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1009 polypeptide havingthe sequence of amino acid residues from about 1 or 23 through about615, inclusive of FIG. 122 (SEQ ID NO:194), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1037] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1009 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1009 antibody.

[1038] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1009 polypeptide, bycontacting the native PRO1009 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1039] In a still further embodiment, the invention concerns acomposition comprising a PRO1009 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1040] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA50853 comprising thenucleotide sequence of FIG. 123 (SEQ ID NO:195).

[1041] 49. PRO1007

[1042] Applicants have identified a cDNA clone that encodes a novelpolypeptide having sequence identity with MAGPIAP, wherein thepolypeptide is designated in the present application as “PRO1007”.

[1043] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1007 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1007polypeptide having amino acid residues 1 through 346 of FIG. 125 (SEQ IDNO:197), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. The isolated nucleic acid sequence maycomprise the cDNA insert of the vector deposited on Jun. 9, 1998 withthe ATCC as DNA57690-1374 which includes the nucleotide sequenceencoding PRO1007.

[1044] In another embodiment, the invention provides isolated PRO1007polypeptide. In particular, the invention provides isolated nativesequence PRO1007 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 346 of FIG. 125 (SEQ IDNO:197). An additional embodiment of the present invention is directedto an isolated extracellular domain of a PRO1007 polypeptide.Optionally, the PRO1007 polypeptide is obtained or is obtainable byexpressing the polypeptide encoded by the cDNA insert of the vectordeposited with the ATCC on Jun. 9, 1998 as DNA57690-1374.

[1045] 50. PRO1056

[1046] A cDNA clone (DNA57693-1424) has been identified, having homologyto nucleic acid encoding a chloride channel protein that encodes a novelpolypeptide, designated in the present application as “PRO1056”.

[1047] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1056 polypeptide.

[1048] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1056 polypeptide having the sequence of aminoacid residues from about 1 or about 19 to about 120, inclusive of FIG.127 (SEQ ID NO:199), or (b) the complement of the DNA molecule of (a).

[1049] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1056 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 56 orabout 110 and about 415, inclusive, of FIG. 126 (SEQ ID NO:198).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1050] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203008 (DNA57693-1424) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203008 (DNA57693-1424).

[1051] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 19 to about 120, inclusive of FIG. 127(SEQ ID NO:199), or (b) the complement of the DNA of (a).

[1052] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1056 polypeptide having the sequence of amino acidresidues from 1 or about 19 to about 120, inclusive of FIG. 127 (SEQ IDNO:199), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1053] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1056 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 18 in thesequence of FIG. 127 (SEQ ID NO:199). The transmembrane domain has beententatively identified as extending from about amino acid position 39 toabout amino acid position 58 in the PRO1056 amino acid sequence (FIG.127, SEQ ID NO:199).

[1054] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199), or (b)the complement of the DNA of (a).

[1055] Another embodiment is directed to fragments of a PRO1056polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 126 (SEQ ID NO:198).

[1056] In another embodiment, the invention provides isolated PRO1056polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1057] In a specific aspect, the invention provides isolated nativesequence PRO1056 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 19 to about 120 ofFIG. 127 (SEQ ID NO:199).

[1058] In another aspect, the invention concerns an isolatedPRO1056polypeptide, comprising an amino acid sequence having at leastabout 80% sequence identity, preferably at least about 85% sequenceidentity, more preferably at least about 90% sequence identity, mostpreferably at least about 95% sequence identity to the sequence of aminoacid residues 1 or about 19 to about 120, inclusive of FIG. 127 (SEQ IDNO:199).

[1059] In a further aspect, the invention concerns an isolated PRO1056polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199).

[1060] In yet another aspect, the invention concerns an isolated PRO1056polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 120, inclusive of FIG. 127 (SEQ ID NO:199), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1056antibody. Preferably, the PRO1056 fragment retains a qualitativebiological activity of a native PRO1056 polypeptide.

[1061] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1056 polypeptide havingthe sequence of amino acid residues from about 1 or about 19 to about120, inclusive of FIG. 127 (SEQ ID NO:199), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1062] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1056 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1056 antibody.

[1063] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1056 polypeptide bycontacting the native PRO1056 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1064] In a still further embodiment, the invention concerns acomposition comprising a PRO1056 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1065] 51. PRO826

[1066] A cDNA clone (DNA57694-1341) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO826”.

[1067] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO826 polypeptide.

[1068] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO826 polypeptide having the sequence of amino acidresidues from about 1 or about 23 to about 99, inclusive of FIG. 129(SEQ ID NO:201), or (b) the complement of the DNA molecule of (a).

[1069] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO826 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 13 orabout 79 and about 309, inclusive, of FIG. 128 (SEQ ID NO:200).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1070] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203017 (DNA57694-1341) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203017 (DNA57694-1341).

[1071] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 23 to about 99, inclusive of FIG. 129(SEQ ID NO:201), or (b) the complement of the DNA of (a).

[1072] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO826 polypeptide having the sequence of amino acid residuesfrom 1 or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1073] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO826 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 22 in the sequence of FIG.129 (SEQ ID NO:201).

[1074] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201), or (b)the complement of the DNA of (a).

[1075] Another embodiment is directed to fragments of a PRO826polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 128 (SEQ ID NO:200).

[1076] In another embodiment, the invention provides isolated PRO826polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1077] In a specific aspect, the invention provides isolated nativesequence PRO826 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 23 to about 99 ofFIG. 129 (SEQ ID NO:201).

[1078] In another aspect, the invention concerns an isolated PRO826polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201).

[1079] In a further aspect, the invention concerns an isolated PRO826polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201).

[1080] In yet another aspect, the invention concerns an isolated PRO826polypeptide, comprising the sequence of amino acid residues 1 or about23 to about 99, inclusive of FIG. 129 (SEQ ID NO:201), or a fragmentthereof sufficient to provide a binding site for an anti-PRO826antibody. Preferably, the PRO826 fragment retains a qualitativebiological activity of a native PRO826 polypeptide.

[1081] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO826 polypeptide havingthe sequence of amino acid residues from about 1 or about 23 to about99, inclusive of FIG. 129 (SEQ ID NO:201), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1082] 52. PRO819

[1083] A cDNA clone (DNA57695-1340) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO819”.

[1084] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO819 polypeptide.

[1085] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO819 polypeptide having the sequence of amino acidresidues from about 1 or about 25 to about 52, inclusive of FIG. 131(SEQ ID NO:203), or (b) the complement of the DNA molecule of (a).

[1086] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO819 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 46 orabout 118 and about 201, inclusive, of FIG. 130 (SEQ ID NO:202).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1087] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203006 (DNA57695-1340) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203006 (DNA57695-1340).

[1088] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 25 to about 52, inclusive of FIG. 131(SEQ ID NO:203), or (b) the complement of the DNA of (a).

[1089] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO819 polypeptide having the sequence of amino acid residuesfrom 1 or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203),or (b) the complement of the DNA molecule of (a), and, if the DNAmolecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1090] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO819 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 24 in the sequence of FIG.131 (SEQ ID NO:203).

[1091] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203), or (b)the complement of the DNA of (a).

[1092] Another embodiment is directed to fragments of a PRO819polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 130 (SEQ ID NO:202).

[1093] In another embodiment, the invention provides isolated PRO819polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1094] In a specific aspect, the invention provides isolated nativesequence PRO819 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 25 to about 52 ofFIG. 131 (SEQ ID NO:203).

[1095] In another aspect, the invention concerns an isolated PRO819polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203).

[1096] In a further aspect, the invention concerns an isolated PRO819polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203).

[1097] In yet another aspect, the invention concerns an isolated PRO819polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 52, inclusive of FIG. 131 (SEQ ID NO:203), or a fragmentthereof sufficient to provide a binding site for an anti-PRO819antibody. Preferably, the PRO819 fragment retains a qualitativebiological activity of a native PRO819 polypeptide.

[1098] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO819 polypeptide havingthe sequence of amino acid residues from about 1 or about 25 to about52, inclusive of FIG. 131 (SEQ ID NO:203), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1099] 53. PRO1006

[1100] A cDNA clone (DNA57699-1412) has been identified, having sequenceidentity with a virud protein believed to be a tyrosine protein kinase,that encodes a novel polypeptide, designated in the present applicationas “PRO1006.”

[1101] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1006 polypeptide.

[1102] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1006 polypeptide having the sequence of aminoacid residues from about 1 or 24 to about 392, inclusive of FIG. 133(SEQ ID NO:205), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to amino or nucleic acids is meant torefer to two alternative embodiments provided herein, i.e., 1-392, or inanother embodiment, 24-392.

[1103] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1006 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 28 or 97and about 1203, inclusive, of FIG. 132 (SEQ ID NO:204). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1104] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203020 (DNA57699-1412), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203020 (DNA57699-1412).

[1105] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 24 to about 392, inclusive of FIG.133 (SEQ ID NO:205), or the complement of the DNA of (a).

[1106] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1006polypeptide having the sequence of amino acid residues from about 1 or24 to about 392, inclusive of FIG. 133 (SEQ ID NO:205), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1107] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 24 to about 392, inclusive of FIG. 133 (SEQ ID NO:205), or (b) thecomplement of the DNA of (a).

[1108] In another embodiment, the invention provides isolated PRO1006polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1109] In a specific aspect, the invention provides isolated nativesequence PRO1006 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 24 through 392 of FIG. 133 (SEQID NO:205).

[1110] In another aspect, the invention concerns an isolated PRO1006polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 24 to about 392, inclusive of FIG. 133 (SEQ ID NO:205).

[1111] In a further aspect, the invention concerns an isolated PRO1006polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 24through 392 of FIG. 133 (SEQ ID NO:205).

[1112] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1006 polypeptide havingthe sequence of amino acid residues from about 1 or 24 to about 392,inclusive of FIG. 133 (SEQ ID NO:205), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1113] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1006 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1006 antibody.

[1114] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1006 polypeptide, bycontacting the native PRO1006 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1115] In a still further embodiment, the invention concerns acomposition comprising a PRO1006 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1116] 54. PRO1112

[1117] Applicants have identified a cDNA clone that encodes a novelpolypeptide having multiple transmembrane domains and having somesequence identity with a Mycobacterium tuberculosis peptide, a peptidefound in a Dayhoff database designated as “MTY20B11_(—)13”, wherein thenovel polypeptide is designated in the present application as “PRO1112”.

[1118] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1112 polypeptide.

[1119] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO112 polypeptide having the sequence of amino acidresidues from 1 or about 14 through about 262 of FIG. 135 (SEQ IDNO:207), or (b) the complement of the DNA molecule of (a).

[1120] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1112 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues about 20 or59 through 809 of FIG. 134 (SEQ ID NO:206). Preferably, hybridizationoccurs under stringent hybridization and wash conditions.

[1121] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in the ATCCDeposit of DNA57702-1476 made on Jun. 9, 1998. In a preferredembodiment, the nucleic acid comprises a DNA encoding the same maturepolypeptide encoded by the human protein cDNA in the ATCC Deposit ofDNA57702-1476 made on Jun. 9, 1998.

[1122] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 14 through about 262 of FIG. 135 (SEQ IDNO:207).

[1123] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1112 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domains deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 13 of FIG. 135(SEQ ID NO:207). The transmembrane domains have been tentativelyidentified as extending from about amino acid positions 58-76, 99-113,141-159 and 203-222 of FIG. 135 (SEQ ID NO:207).

[1124] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 14 through 262 of FIG. 135 (SEQ ID NO:207).

[1125] Another embodiment is directed to fragments of a PRO112polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 60 to about 100 nucleotidesin length.

[1126] In another embodiment, the invention provides isolated PRO112polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1127] In a specific aspect, the invention provides isolated nativesequence PRO112 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 14 through about 262 of FIG. 135(SEQ ID NO:207).

[1128] In another aspect, the invention concerns an isolated PRO112polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 14 through about 262 of FIG. 135 (SEQ ID NO:207).

[1129] In a further aspect, the invention concerns an isolated PRO1112polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 14 through about 262 of FIG. 135 (SEQ ID NO:207).

[1130] In yet another aspect, the invention concerns an isolated PRO1112polypeptide, comprising the sequence of amino acid residues 1 or about14 through about 262 of FIG. 135 (SEQ ID NO:207), or a fragment thereofsufficient to provide a binding site for an anti-PRO1112 antibody.Preferably, the PRO1112 fragment retains a qualitative biologicalactivity of a native PRO1112 polypeptide.

[1131] In another aspect, the present invention is directed to fragmentsof a PRO1112 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1132] 55. PRO1074

[1133] Applicants have identified a cDNA clone, DNA57704-1452, thatencodes a novel polypeptide having homology to galactosyltransferase,wherein the polypeptide is designated in the present application as“PRO1074”.

[1134] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1074 polypeptide.

[1135] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1074 polypeptide having the sequence of aminoacid residues from 1 to about 331, inclusive of FIG. 137 (SEQ IDNO:209), or (b) the complement of the DNA molecule of (a).

[1136] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1074 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid sequence having aboutresidues 322 to 1314, inclusive of FIG. 136 (SEQ ID NO:208). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1137] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209953 (DNA57704-1452), which was deposited on Jun. 9, 1998,or (b) the complement of the DNA molecule of (a).

[1138] In a preferred embodiment, the nucleic acid comprises a DNAmolecule encoding the same mature polypeptide encoded by the humanprotein cDNA in ATCC Deposit No. 209953 (DNA57704-1452).

[1139] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to the sequenceof amino acid residues 1 to about 331, inclusive of FIG. 137 (SEQ IDNO:209).

[1140] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1074 extracellular domain(ECD), with or without the initiating methionine, and its solublevariants (i.e. transmembrane domain(s) deleted or inactivated) or iscomplementary to such encoding nucleic acid molecule. A type IItransmembrane domain region has been tentatively identified as extendingfrom about amino acid position 20 to 39 in the PRO1074 amino acidsequence (FIG. 137, SEQ ID NO:209).

[1141] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 to about 331, inclusive of FIG. 137 (SEQ IDNO:209).

[1142] Another embodiment is directed to fragments of a PRO1074polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1143] In another embodiment, the invention provides isolated PRO1074polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1144] In a specific aspect, the invention provides isolated nativesequence PRO1074 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 331 of FIG. 137 (SEQ ID NO:209).

[1145] In another aspect, the invention concerns an isolated PRO1074polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to 331, inclusive of FIG. 137 (SEQ ID NO:209).

[1146] In a further aspect, the invention concerns an isolated PRO1074polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 331 of FIG. 137 (SEQ ID NO:209).

[1147] In another aspect, the invention concerns a PRO1074 extracellulardomain comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residuesX to 331 of FIG. 2 (SEQ ID NO:3), wherein X is any one of amino acidresidues 35 to 44 of FIG. 137 (SEQ ID NO:209).

[1148] In yet another aspect, the invention concerns an isolated PRO1074polypeptide, comprising the sequence of amino acid residues 1 to about331, inclusive of FIG. 137 (SEQ ID NO:209), or a fragment thereofsufficient to provide a binding site for an anti-PRO1074 antibody.Preferably, the PRO1074 fragment retains a qualitative biologicalactivity of a native PRO1074 polypeptide.

[1149] In another aspect, the present invention is directed to fragmentsof a PRO1074 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1150] In yet another embodiment, the invention concerns agonist andantagonists of the PRO1074 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1074 antibody.

[1151] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1074 polypeptide.

[1152] In still a further embodiment, the invention concerns acomposition comprising a PRO1074 polypeptide as hereinabove defined, incombination with a pharmaceutically acceptable carrier.

[1153] 56. PRO1005

[1154] A cDNA clone (DNA57708-1411) has been identified that encodes anovel polypeptide, designated in the present application as “PRO1005.”

[1155] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1005 polypeptide.

[1156] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1005 polypeptide having the sequence of aminoacid residues from about 21 to about 185, inclusive of FIG. 139 (SEQ IDNO:211), or (b) the complement of the DNA molecule of (a).

[1157] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1005 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 90 andabout 584, inclusive, of FIG. 138 (SEQ ID NO:210). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1158] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203021 (DNA57708-1411), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203021 (DNA57708-1411).

[1159] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 21 to about 185, inclusive of FIG. 139(SEQ ID NO:211), or the complement of the DNA of (a).

[1160] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 50 nucleotides, and preferably at least100 nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1005polypeptide having the sequence of amino acid residues from about 21 toabout 185, inclusive of FIG. 139 (SEQ ID NO:211), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[1161] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1005 polypeptide, with orwithout the N-terminal signal sequence, or is complementary to suchencoding nucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 through about aminoacid position 20 in the sequence of FIG. 139 (SEQ ID NO:211).

[1162] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 185, inclusive of FIG. 139 (SEQ ID NO:211), or (b) thecomplement of the DNA of (a).

[1163] Another embodiment is directed to fragments of a PRO1005polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1164] In another embodiment, the invention provides isolated PRO1005polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1165] In a specific aspect, the invention provides isolated nativesequence PRO1005 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 21 to 185 of FIG. 139 (SEQ ID NO:211).

[1166] In another aspect, the invention concerns an isolated PRO1005polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 185, inclusive of FIG. 139 (SEQ ID NO:211).

[1167] In a further aspect, the invention concerns an isolated PRO1005polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to185 of FIG. 139 (SEQ ID NO:211).

[1168] In yet another aspect, the invention concerns an isolated PRO1005polypeptide, comprising the sequence of amino acid residues 21 to about185, inclusive of FIG. 139 (SEQ ID NO:211), or a fragment thereofsufficient to provide a binding site for an anti-PRO1005 antibody.Preferably, the PRO1005 fragment retains a qualitative biologicalactivity of a native PRO1005 polypeptide.

[1169] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1005 polypeptide havingthe sequence of amino acid residues from about 21 to about 185,inclusive of FIG. 139 (SEQ ID NO:211), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1170] 57. PRO1073

[1171] A cDNA clone (DNA57710-1451) has been identified that encodes anovel polypeptide, designated in the present application as “PRO1073.”

[1172] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1073 polypeptide.

[1173] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1073 polypeptide having the sequence of aminoacid residues from about 32 to about 299, inclusive of FIG. 141 (SEQ IDNO:213), or (b) the complement of the DNA molecule of (a).

[1174] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1073 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 438 andabout 1241, inclusive, of FIG. 140 (SEQ ID NO:212). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1175] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203048 (DNA57710-1451), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203048 (DNA57710-1451).

[1176] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 32 to about 299, inclusive of FIG. 141(SEQ ID NO:213), or the complement of the DNA of (a).

[1177] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1073 polypeptide having the sequence of amino acid residues fromabout 32 to about 299, inclusive of FIG. 141 (SEQ ID NO:213), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1178] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1073 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 31 in the sequence of FIG.141 (SEQ ID NO:213).

[1179] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 32to about 299, inclusive of FIG. 141 (SEQ ID NO:213), or (b) thecomplement of the DNA of (a).

[1180] Another embodiment is directed to fragments of a PRO1073polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1181] In another embodiment, the invention provides isolated PRO1073polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1182] In a specific aspect, the invention provides isolated nativesequence PRO1073 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 32 to 299 of FIG. 141 (SEQ ID NO:213).

[1183] In another aspect, the invention concerns an isolated PRO1073polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues32 to about 299, inclusive of FIG. 141 (SEQ ID NO:213).

[1184] In a further aspect, the invention concerns an isolated PRO1073polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 32 to299 of FIG. 141 (SEQ ID NO:213).

[1185] In yet another aspect, the invention concerns an isolated PRO1073polypeptide, comprising the sequence of amino acid residues 32 to about299, inclusive of FIG. 141 (SEQ ID NO:213), or a fragment thereofsufficient to provide a binding site for an anti-PRO1073 antibody.Preferably, the PRO1073 fragment retains a qualitative biologicalactivity of a native PRO1073 polypeptide.

[1186] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1073 polypeptide havingthe sequence of amino acid residues from about 32 to about 299,inclusive of FIG. 141 (SEQ ID NO:213), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1187] 58. PRO1152

[1188] A cDNA clone (DNA57711-1501) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO1152”.

[1189] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1152 polypeptide.

[1190] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1152 polypeptide having the sequence of aminoacid residues from about 1 or about 29 to about 479, inclusive of FIG.144 (SEQ ID NO:216), or (b) the complement of the DNA molecule of (a).

[1191] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1152 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 58 orabout 142 and about 1494, inclusive, of FIG. 143 (SEQ ID NO:215).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1192] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203047 (DNA57711-1501) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203047 (DNA57711-1501).

[1193] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 29 to about 479, inclusive of FIG. 144(SEQ ID NO:216), or (b) the complement of the DNA of (a).

[1194] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 300 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1152 polypeptide having the sequence of aminoacid residues from 1 or about 29 to about 479, inclusive of FIG. 144(SEQ ID NO:216), or (b) the complement of the DNA molecule of (a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[1195] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1152 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 28 in thesequence of FIG. 144 (SEQ ID NO:216). The various transmembrane domainshave been tentatively identified as extending from about amino acidposition 133 to about amino acid position 155, from about amino acidposition 168 to about amino acid position 187, from about amino acidposition 229 to about amino acid position 247, from about amino acidposition 264 to about amino acid position 285, from about amino acidposition 309 to about amino acid position 330, from about amino acidposition 371 to about amino acid position 390 and from about amino acidposition 441 to about amino acid position 464 in the PRO1152 amino acidsequence (FIG. 144, SEQ ID NO:216).

[1196] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216), or (b)the complement of the DNA of (a).

[1197] Another embodiment is directed to fragments of a PRO1152polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 143 (SEQ ID NO:215).

[1198] In another embodiment, the invention provides isolated PRO1152polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1199] In a specific aspect, the invention provides isolated nativesequence PRO1152 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 29 to about 479 ofFIG. 144 (SEQ ID NO:216).

[1200] In another aspect, the invention concerns an isolated PRO1152polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216).

[1201] In a further aspect, the invention concerns an isolated PRO1152polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216).

[1202] In yet another aspect, the invention concerns an isolated PRO1152polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 479, inclusive of FIG. 144 (SEQ ID NO:216), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1152antibody. Preferably, the PRO1152 fragment retains a qualitativebiological activity of a native PRO1152 polypeptide.

[1203] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1152 polypeptide havingthe sequence of amino acid residues from about 1 or about 29 to about479, inclusive of FIG. 144 (SEQ ID NO:216), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1204] In another embodiment, the invention provides a nucleic aidmolecule designated herein as DNA55807 comprising the nucleotidesequence of SEQ ID NO:217 (see FIG. 145).

[1205] 59. PRO1136

[1206] A cDNA clone (DNA57827-1493) has been identified, having homologyto nucleic acid encoding PDZ domain-containing proteins that encodes anovel polypeptide, designated in the present application as “PRO1136”.

[1207] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1136 polypeptide.

[1208] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1136 polypeptide having the sequence of aminoacid residues from about 1 or about 16 to about 632, inclusive of FIG.147 (SEQ ID NO:219), or (b) the complement of the DNA molecule of (a).

[1209] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1136 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 216 orabout 261 and about 2111, inclusive, of FIG. 146 (SEQ ID NO:218).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1210] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203045 (DNA57827-1493) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203045 (DNA57827-1493).

[1211] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 16 to about 632, inclusive of FIG. 147(SEQ ID NO:219), or (b) the complement of the DNA of (a).

[1212] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1136 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 632, inclusive of FIG. 147 (SEQ IDNO:219), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1213] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1136 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 15 in the sequence of FIG.147 (SEQ ID NO:219).

[1214] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219), or (b)the complement of the DNA of (a).

[1215] Another embodiment is directed to fragments of a PRO1136polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 146 (SEQ ID NO:218).

[1216] In another embodiment, the invention provides isolated PRO1136polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1217] In a specific aspect, the invention provides isolated nativesequence PRO1136 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 16 to about 632 ofFIG. 147 (SEQ ID NO:219).

[1218] In another aspect, the invention concerns an isolated PRO1136polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219).

[1219] In a further aspect, the invention concerns an isolated PRO1136polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219).

[1220] In yet another aspect, the invention concerns an isolated PRO1136polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 632, inclusive of FIG. 147 (SEQ ID NO:219), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1136antibody. Preferably, the PRO1136 fragment retains a qualitativebiological activity of a native PRO1136 polypeptide.

[1221] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1136 polypeptide havingthe sequence of amino acid residues from about 1 or about 16 to about632, inclusive of FIG. 147 (SEQ ID NO:219), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1222] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1136 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1136 antibody.

[1223] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1136 polypeptide bycontacting the native PRO1136 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1224] In a still further embodiment, the invention concerns acomposition comprising a PRO1136 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1225] 60. PRO813

[1226] Applicants have identified a cDNA clone (DNA57834-1339) havinghomology to pulmonary surfactant-associated protein C that encodes anovel polypeptide, designated in the present application as “PRO813”.

[1227] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO813 polypeptide.

[1228] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO813 polypeptide having the sequence of amino acidresidues from about 1 or about 27 to about 176, inclusive of FIG. 149(SEQ ID NO:221), or (b) the complement of the DNA molecule of (a).

[1229] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO813 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 109 orabout 187 and about 636, inclusive, of FIG. 148 (SEQ ID NO:220).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1230] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209954 (DNA57834-1339). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209954(DNA57834-1339).

[1231] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 27 to about 176, inclusive of FIG. 149(SEQ ID NO:221).

[1232] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO813 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 26 in the sequence of FIG.149 (SEQ ID NO:221).

[1233] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

[1234] Another embodiment is directed to fragments of a PRO813polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1235] In another embodiment, the invention provides isolated PRO813polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1236] In a specific aspect, the invention provides isolated nativesequence PRO813 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 27 to about 176 of FIG. 149(SEQ ID NO:221).

[1237] In another aspect, the invention concerns an isolated PRO813polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

[1238] Ina further aspect, the invention concerns an isolated PRO813polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221).

[1239] In yet another aspect, the invention concerns an isolated PRO813polypeptide, comprising the sequence of amino acid residues 1 or about27 to about 176, inclusive of FIG. 149 (SEQ ID NO:221), or a fragmentthereof sufficient to provide a binding site for an anti-PRO813antibody. Preferably, the PRO813 fragment retains a qualitativebiological activity of a native PRO813 polypeptide.

[1240] In another aspect, the present invention is directed to fragmentsof a PRO813 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1241] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO813 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO813 antibody.

[1242] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO813 polypeptide.

[1243] In still a further embodiment, the invention concerns acomposition comprising a PRO813 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1244] 61. PRO809

[1245] A cDNA clone (DNA57836-1338) has been identified, having sequenceidentity with heparan sulfate proteoglycans, that encodes a novelpolypeptide, designated in the present application as “PRO809.”

[1246] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO809 polypeptide.

[1247] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO809 polypeptide having the sequence of amino acidresidues from about 1 or 19 to about 265, inclusive of FIG. 151 (SEQ IDNO:223), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-265, or in anotherembodiment, 19-265.

[1248] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO809 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 63 or 117and about 867, inclusive, of FIG. 150 (SEQ ID NO:222). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1249] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203025 (DNA57836-1338), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203025 (DNA57836-1338).

[1250] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 19 to about 265, inclusive of FIG.151 (SEQ ID NO:223), or the complement of the DNA of (a).

[1251] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO809polypeptide having the sequence of amino acid residues from about 1 or19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1252] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223), or (b) thecomplement of the DNA of (a).

[1253] In another embodiment, the invention provides isolated PRO809polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1254] In a specific aspect, the invention provides isolated nativesequence PRO809 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 19 through 265 of FIG. 151 (SEQID NO:223).

[1255] In another aspect, the invention concerns an isolated PRO809polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 265, inclusive of FIG. 151 (SEQ ID NO:223).

[1256] In a further aspect, the invention concerns an isolated PRO809polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 265 of FIG. 151 (SEQ ID NO:223).

[1257] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO809 polypeptide havingthe sequence of amino acid residues from about 1 or 19 to about 265,inclusive of FIG. 151 (SEQ ID NO:223), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1258] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO809 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO809 antibody.

[1259] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO809 polypeptide, bycontacting the native PRO809 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1260] In a still further embodiment, the invention concerns acomposition comprising a PRO809 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1261] 62. PRO791

[1262] A cDNA clone (DNA57838-1337) has been identified, having sequenceidentity with MHC class I antigens that encodes a novel polypeptide,designated in the present application as “PRO791.”

[1263] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO791 polypeptide.

[1264] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO791 polypeptide having the sequence of amino acidresidues from about 1 or 26 to about 246, inclusive of FIG. 153 (SEQ IDNO:225), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-246, or in anotherembodiment, 26-246.

[1265] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO791 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 9 or 84 andabout 746, inclusive, of FIG. 152 (SEQ ID NO:224). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1266] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203014 (DNA57838-1337), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203014 (DNA57838-1337).

[1267] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 26 to about 246, inclusive of FIG.153 (SEQ ID NO:225), or the complement of the DNA of (a).

[1268] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO791polypeptide having the sequence of amino acid residues from about 1 or26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1269] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225), or (b) thecomplement of the DNA of (a).

[1270] In another embodiment, the invention provides isolated PRO791polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1271] In a specific aspect, the invention provides isolated nativesequence PRO791 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 26 through 246 of FIG. 153 (SEQID NO:225).

[1272] In another aspect, the invention concerns an isolated PRO791polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 246, inclusive of FIG. 153 (SEQ ID NO:225).

[1273] In a further aspect, the invention concerns an isolated PRO791polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 246 of FIG. 153 (SEQ ID NO:225).

[1274] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO791 polypeptide havingthe sequence of amino acid residues from about 1 or 26 to about 246,inclusive of FIG. 153 (SEQ ID NO:225), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1275] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO791 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO791 antibody.

[1276] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO791 polypeptide, bycontacting the native PRO791 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1277] In a still further embodiment, the invention concerns acomposition comprising a PRO791 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1278] 63. PRO1004

[1279] A cDNA clone (DNA57844-1410) has been identified that encodes anovel polypeptide, designated in the present application as “PRO1004.”

[1280] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1004 polypeptide.

[1281] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1004 polypeptide having the sequence of aminoacid residues from about 25 to about 115, inclusive of FIG. 155 (SEQ IDNO:227), or (b) the complement of the DNA molecule of (a).

[1282] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1004 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 191 andabout 463, inclusive, of FIG. 154 (SEQ ID NO:226). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1283] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203010 (DNA57844-1410), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203010 (DNA57844-1410).

[1284] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 25 to about 115, inclusive of FIG. 155(SEQ ID NO:227), or the complement of the DNA of (a).

[1285] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 50 nucleotides, and preferably at least100 nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1004polypeptide having the sequence of amino acid residues from about 25 toabout 115, inclusive of FIG. 155 (SEQ ID NO:227), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[1286] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1004 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 through about amino acid position 24 in the sequence ofFIG. 155 (SEQ ID NO:227).

[1287] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 25to about 115, inclusive of FIG. 155 (SEQ ID NO:227), or (b) thecomplement of the DNA of (a).

[1288] Another embodiment of the invention is directed to fragments of aPRO1004 polypeptide coding sequence that may find use as hybridizationprobes. Such nucleic acid fragments are from about 20 to about 80nucleotides in length, preferably from about 20 to about 60 nucleotidesin length, more preferably from about 20 to about 50 nucleotides inlength, and most preferably from about 20 to about 40 nucleotides inlength.

[1289] In another embodiment, the invention provides isolated PRO1004polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1290] In a specific aspect, the invention provides isolated nativesequence PRO1004 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 25 to 115 of FIG. 155 (SEQ ID NO:227).

[1291] In another aspect, the invention concerns an isolated PRO1004polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues25 to about 115, inclusive of FIG. 155 (SEQ ID NO:227).

[1292] In a further aspect, the invention concerns an isolated PRO1004polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 25 to115 of FIG. 155 (SEQ ID NO:227).

[1293] In yet another aspect, the invention concerns an isolated PRO1004polypeptide, comprising the sequence of amino acid residues 25 to about115, inclusive of FIG. 155 (SEQ ID NO:227), or a fragment thereofsufficient to provide a binding site for an anti-PRO1004 antibody.Preferably, the PRO1004 fragment retains a qualitative biologicalactivity of a native PRO1004 polypeptide.

[1294] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1004 polypeptide havingthe sequence of amino acid residues from about 25 to about 115,inclusive of FIG. 155 (SEQ ID NO:227), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1295] 64. PRO1111

[1296] A cDNA clone (DNA58721-1475) has been identified that encodes anovel polypeptide having sequence identity with LIG and designated inthe present application as “PRO1111.”

[1297] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1111 polypeptide.

[1298] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1111 polypeptide having the sequence of aminoacid residues from about 1 to about 653, inclusive of FIG. 157 (SEQ IDNO:229), or (b) the complement of the DNA molecule of (a).

[1299] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1111 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 57 andabout 2015, inclusive, of FIG. 156 (SEQ ID NO:228). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1300] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203110 (DNA58721-1475), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203110 (DNA58721-1475).

[1301] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 653, inclusive of FIG. 157(SEQ ID NO:229), or the complement of the DNA of (a).

[1302] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1111 polypeptide having the sequence of amino acid residues fromabout 1 to about 653, inclusive of FIG. 157 (SEQ ID NO:229), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1303] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1111 polypeptide in itssoluble form, i.e. transmembrane domain deleted or inactivated variants,or is complementary to such encoding nucleic acid molecule. Thetransmembrane domains has been tentatively identified as extending fromabout amino acid positions 21-40 (type II) and 528-548 in the PRO1111amino acid sequence (FIG. 157, SEQ ID NO:229).

[1304] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 653, inclusive of FIG. 157 (SEQ ID NO:229), or (b) thecomplement of the DNA of (a).

[1305] Another embodiment is directed to fragments of a PRO1111polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1306] In another embodiment, the invention provides isolated PRO1111polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1307] In a specific aspect, the invention provides isolated nativesequence PRO1111 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 653 of FIG. 157 (SEQ IDNO:229).

[1308] In another aspect, the invention concerns an isolated PRO1111polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 653, inclusive of FIG. 157 (SEQ ID NO:229).

[1309] In a further aspect, the invention concerns an isolated PRO1111polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 653 of FIG. 157 (SEQ ID NO:229).

[1310] In yet another aspect, the invention concerns an isolated PRO1111polypeptide, comprising the sequence of amino acid residues 1 to about653, inclusive of FIG. 157 (SEQ ID NO:229), or a fragment thereofsufficient to provide a binding site for an anti-PRO1111 antibody.Preferably, the PRO1111 fragment retains a qualitative biologicalactivity of a native PRO1111 polypeptide.

[1311] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1111 polypeptide havingthe sequence of amino acid residues from about 1 to about 653, inclusiveof FIG. 157 (SEQ ID NO:229), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1312] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1111 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1111 antibody.

[1313] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1111 polypeptide, bycontacting the native PRO1111 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1314] In a still further embodiment, the invention concerns acomposition comprising a PRO1111 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1315] 65. PRO1344

[1316] A cDNA clone (DNA58723-1588) has been identified, having homologyto nucleic acid encoding factor C that encodes a novel polypeptide,designated in the present application as “PRO1344”.

[1317] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1344 polypeptide.

[1318] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1344 polypeptide having the sequence of aminoacid residues from about 1 or about 24 to about 720, inclusive of FIG.159 (SEQ ID NO:231), or (b) the complement of the DNA molecule of (a).

[1319] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1344 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 26 orabout 95 and about 2185, inclusive, of FIG. 158 (SEQ ID NO:230).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1320] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203133 (DNA58723-1588) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203133 (DNA58723-1588).

[1321] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 24 to about 720, inclusive of FIG. 159(SEQ ID NO:231), or (b) the complement of the DNA of (a).

[1322] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1344 polypeptide having the sequence of amino acidresidues from 1 or about 24 to about 720, inclusive of FIG. 159 (SEQ IDNO:231), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1323] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1344 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 23 in the sequence of FIG.159 (SEQ ID NO:231).

[1324] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231), or (b)the complement of the DNA of (a).

[1325] Another embodiment is directed to fragments of a PRO1344polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 158 (SEQ ID NO:230).

[1326] In another embodiment, the invention provides isolated PRO1344polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1327] In a specific aspect, the invention provides isolated nativesequence PRO1344 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 24 to about 720 ofFIG. 159 (SEQ ID NO:231).

[1328] In another aspect, the invention concerns an isolated PRO1344polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231).

[1329] In a further aspect, the invention concerns an isolated PRO1344polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231).

[1330] In yet another aspect, the invention concerns an isolated PRO1344polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 720, inclusive of FIG. 159 (SEQ ID NO:231), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1344antibody. Preferably, the PRO1344 fragment retains a qualitativebiological activity of a native PRO1344 polypeptide.

[1331] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1344 polypeptide havingthe sequence of amino acid residues from about 1 or about 24 to about720, inclusive of FIG. 159 (SEQ ID NO:231), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1332] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1344 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1344 antibody.

[1333] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1344 polypeptide bycontacting the native PRO1344 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1334] In a still further embodiment, the invention concerns acomposition comprising a PRO1344 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1335] 66. PRO1109

[1336] A cDNA clone (DNA58737-1473) has been identified, having homologyto nucleic acid encoding β-1,4-galactosyltransferase, that encodes anovel polypeptide, designated in the present application as “PRO1109”.

[1337] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1109 polypeptide.

[1338] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1109 polypeptide having the sequence of aminoacid residues from about 1 or about 28 to about 344, inclusive of FIG.161 (SEQ ID NO:236), or (b) the complement of the DNA molecule of (a).

[1339] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1109 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 119 orabout 200 and about 1150, inclusive, of FIG. 160 (SEQ ID NO:235).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1340] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203136 (DNA58737-1473) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203136 (DNA58737-1473).

[1341] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 28 to about 344, inclusive of FIG. 161(SEQ ID NO:236), or (b) the complement of the DNA of (a).

[1342] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1109 polypeptide having the sequence of amino acidresidues from 1 or about 28 to about 344, inclusive of FIG. 161 (SEQ IDNO:236), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1343] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1109 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 27 in the sequence of FIG.161 (SEQ ID NO:236).

[1344] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236), or (b)the complement of the DNA of (a).

[1345] Another embodiment is directed to fragments of a PRO1109polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 160 (SEQ ID NO:235).

[1346] In another embodiment, the invention provides isolated PRO1109polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1347] In a specific aspect, the invention provides isolated nativesequence PRO1109 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 28 to about 344 ofFIG. 161 (SEQ ID NO:236).

[1348] In another aspect, the invention concerns an isolated PRO1109polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236).

[1349] In a further aspect, the invention concerns an isolated PRO1109polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236).

[1350] In yet another aspect, the invention concerns an isolated PRO1109polypeptide, comprising the sequence of amino acid residues 1 or about28 to about 344, inclusive of FIG. 161 (SEQ ID NO:236), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1109antibody. Preferably, the PRO1109 fragment retains a qualitativebiological activity of a native PRO1109 polypeptide.

[1351] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1109 polypeptide havingthe sequence of amino acid residues from about 1 or about 28 to about344, inclusive of FIG. 161 (SEQ ID NO:236), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1352] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1109 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1109 antibody.

[1353] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1109 polypeptide bycontacting the native PRO1109 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1354] In a still further embodiment, the invention concerns acomposition comprising a PRO1109 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1355] 67. PRO1383

[1356] A cDNA clone (DNA58743-1609) has been identified, having homologyto nucleic acid encoding the human melanoma cell-expressed protein nmb,that encodes a novel polypeptide, designated in the present applicationas “PRO1383”.

[1357] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1383 polypeptide.

[1358] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1383 polypeptide having the sequence of aminoacid residues from about 1 or about 25 to about 423, inclusive of FIG.163 (SEQ ID NO:241), or (b) the complement of the DNA molecule of (a).

[1359] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1383 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 122 orabout 194 and about 1390, inclusive, of FIG. 162 (SEQ ID NO:240).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1360] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203154 (DNA58743-1609) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203154 (DNA58743-1609).

[1361] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 25 to about 423, inclusive of FIG. 163(SEQ ID NO:241), or (b) the complement of the DNA of (a).

[1362] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1383 polypeptide having the sequence of amino acidresidues from 1 or about 25 to about 423, inclusive of FIG. 163 (SEQ IDNO:241), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1363] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1383 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 24 in thesequence of FIG. 163 (SEQ ID NO:241). The transmembrane domain has beententatively identified as extending from about amino acid position 339to about amino acid position 362 in the PRO1383 amino acid sequence(FIG. 163, SEQ ID NO:241).

[1364] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241), or (b)the complement of the DNA of (a).

[1365] Another embodiment is directed to fragments of a PRO1383polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 162 (SEQ ID NO:240).

[1366] In another embodiment, the invention provides isolated PRO1383polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1367] In a specific aspect, the invention provides isolated nativesequence PRO1383 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 25 to about 423 ofFIG. 163 (SEQ ID NO:241).

[1368] In another aspect, the invention concerns an isolated PRO1383polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241).

[1369] In a further aspect, the invention concerns an isolated PRO1383polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241).

[1370] In yet another aspect, the invention concerns an isolated PRO1383polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 423, inclusive of FIG. 163 (SEQ ID NO:241), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1383antibody. Preferably, the PRO1383 fragment retains a qualitativebiological activity of a native PRO1383 polypeptide.

[1371] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1383 polypeptide havingthe sequence of amino acid residues from about 1 or about 25 to about423, inclusive of FIG. 163 (SEQ ID NO:241), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1372] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1383 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1383 antibody.

[1373] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1383 polypeptide bycontacting the native PRO1383 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1374] In a still further embodiment, the invention concerns acomposition comprising a PRO1383 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1375] 68. PRO1003

[1376] Applicants have identified a cDNA clone, DNA58846-1409, thatencodes a novel secreted polypeptide wherein the polypeptide isdesignated in the present application as “PRO1003”.

[1377] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1003 polypeptide.

[1378] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1003 polypeptide having the sequence of aminoacid residues from 1 or about 25 to about 84, inclusive of FIG. 165 (SEQID NO:246), or (b) the complement of the DNA molecule of (a).

[1379] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1003 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid between about residues41 or about 113 and about 292 inclusive of FIG. 164 (SEQ ID NO:245).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1380] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209957 (DNA58846-1409), which was deposited on Jun. 9, 1998.In a preferred embodiment, the nucleic acid comprises a DNA moleculeencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209957 (DNA58846-1409).

[1381] In an additional aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 25 to about 84, inclusive of FIG. 165(SEQ ID NO:246).

[1382] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 25 to about 84, inclusive of FIG.165 (SEQ ID NO:246).

[1383] Another embodiment is directed to fragments of a PRO1003polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1384] In another embodiment, the invention provides isolated PRO1003polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1385] In a specific aspect, the invention provides isolated nativesequence PRO1003 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 25 to 84 of FIG. 165 (SEQID NO:246).

[1386] In another aspect, the invention concerns an isolated PRO1003polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to 84, inclusive of FIG. 165 (SEQ ID NO:246).

[1387] In a further aspect, the invention concerns an isolated PRO1003polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 84 of FIG. 165 (SEQ ID NO:246).

[1388] In yet another aspect, the invention concerns an isolated PRO1003polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 84, inclusive of FIG. 165 (SEQ ID NO:246), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1003antibody. Preferably, the PRO1003 fragment retains a qualitativebiological activity of a native PRO1003 polypeptide.

[1389] In another aspect, the present invention is directed to fragmentsof a PRO1003 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1390] 69. PRO1108

[1391] Applicants have identified a cDNA clone (DNA58848-1472) havinghomology to nucleic acid encoding the LPAAT protein that encodes a novelpolypeptide, designated in the present application as “PRO1108”.

[1392] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1108 polypeptide.

[1393] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1108 polypeptide having the sequence of aminoacid residues from about 1 to about 456, inclusive of FIG. 167 (SEQ IDNO:248), or (b) the complement of the DNA molecule of (a).

[1394] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1108 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 77 andabout 1444, inclusive, of FIG. 166 (SEQ ID NO:247). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1395] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209955 (DNA58848-1472). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209955(DNA58848-1472).

[1396] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 to about 456, inclusive of FIG. 167 (SEQ IDNO:248).

[1397] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1108 polypeptide, with orwithout the initiating methionine, and its soluble, i.e., transmembranedomain deleted or inactivated variants, or is complementary to suchencoding nucleic acid molecule. The transmembrane domains have beententatively identified as being type II domains extending from aboutamino acid position 22 to about amino acid position 42, from about aminoacid position 156 to about amino acid position 176, from about aminoacid position 180 to about amino acid position 199 and from about aminoacid position 369 to about amino acid position 388 in the PRO1108 aminoacid sequence (FIG. 167, SEQ ID NO:248).

[1398] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 456, inclusive of FIG. 167 (SEQ ID NO:248).

[1399] Another embodiment is directed to fragments of a PRO1108polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1400] In another embodiment, the invention provides isolated PRO1108polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1401] In a specific aspect, the invention provides isolated nativesequence PRO1108 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to about 456 of FIG. 167 (SEQ IDNO:248).

[1402] In another aspect, the invention concerns an isolated PRO1108polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 456, inclusive of FIG. 167 (SEQ ID NO:248).

[1403] In a further aspect, the invention concerns an isolated PRO1108polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 456, inclusive of FIG. 167 (SEQ ID NO:248).

[1404] In yet another aspect, the invention concerns an isolated PRO1108polypeptide, comprising the sequence of amino acid residues 1 to about456, inclusive of FIG. 167 (SEQ ID NO:248), or a fragment thereofsufficient to provide a binding site for an anti-PRO1108 antibody.Preferably, the PRO1108 fragment retains a qualitative biologicalactivity of a native PRO1108 polypeptide.

[1405] In another aspect, the present invention is directed to fragmentsof a PRO1108 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1406] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1108 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1108 antibody.

[1407] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1108 polypeptide.

[1408] In still a further embodiment, the invention concerns acomposition comprising a PRO1108 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1409] 70. PRO1137

[1410] Applicants have identified a cDNA clone, DNA58849-1494, thatencodes a novel polypeptide having homology to ribosyltransferasewherein the polypeptide is designated in the present application as“PRO1137”.

[1411] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1137 polypeptide.

[1412] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1137 polypeptide having the sequence of aminoacid residues from 1 or about 15 to about 240, inclusive of FIG. 169(SEQ ID NO:250), or (b) the complement of the DNA molecule of (a).

[1413] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1137 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid sequence having aboutresidues 77 or about 119 to about 796, inclusive of FIG. 168 (SEQ IDNO:249). Preferably, hybridization occurs under stringent hybridizationand wash conditions.

[1414] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209958 (DNA58849-1494), which was deposited on Jun. 9, 1998,or (b) the complement of the DNA molecule of (a).

[1415] In a preferred embodiment, the nucleic acid comprises a DNAmolecule encoding the same mature polypeptide encoded by the humanprotein cDNA in ATCC Deposit No. 209958 (DNA58849-1494).

[1416] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to the sequenceof amino acid residues 1 or about 15 to about 240, inclusive of FIG. 169(SEQ ID NO:250).

[1417] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1137 polypeptide with orwithout the N-terminal signal sequence and/or the initiating methionine,or the complement of such encoding DNA molecule. The signal peptide hasbeen tentatively identified as extending from about amino acid position1 to about amino acid position 14 in the sequence of FIG. 169 (SEQ IDNO:250).

[1418] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 15 to about 240, inclusive of FIG.169 (SEQ ID NO:250).

[1419] Another embodiment is directed to fragments of a PRO1137polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1420] In another embodiment, the invention provides isolated PRO1137polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1421] In a specific aspect, the invention provides isolated nativesequence PRO1137 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 15 to 240 of FIG. 169 (SEQID NO:250).

[1422] In another aspect, the invention concerns an isolated PRO1137polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 15 to 240, inclusive of FIG. 169 (SEQ ID NO:250).

[1423] In a further aspect, the invention concerns an isolated PRO1137polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 15 to about 240 of FIG. 169 (SEQ ID NO:250).

[1424] In yet another aspect, the invention concerns an isolated PRO1137polypeptide, comprising the sequence of amino acid residues 1 or about15 to about 240, inclusive of FIG. 169 (SEQ ID NO:250), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1137antibody. Preferably, the PRO1137 fragment retains a qualitativebiological activity of a native PRO1137 polypeptide.

[1425] In another aspect, the present invention is directed to fragmentsof a PRO1137 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1426] In yet another embodiment, the invention concerns agonist andantagonists of the PRO1137 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1137 antibody.

[1427] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1137 polypeptide.

[1428] In still a further embodiment, the invention concerns acomposition comprising a PRO1137 polypeptide as hereinabove defined, incombination with a pharmaceutically acceptable carrier.

[1429] 71. PRO1138

[1430] Applicants have identified a cDNA clone, DNA58850-1495, thatencodes a novel polypeptide having homology to CD84 leukocyte antigenwherein the polypeptide is designated in the present application as“PRO1138”.

[1431] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1138 polypeptide.

[1432] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1138 polypeptide having the sequence of aminoacid residues from 1 or about 23 to about 335, inclusive of FIG. 171(SEQ ID NO:253), or (b) the complement of the DNA molecule of (a).

[1433] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1138 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid sequence having aboutresidues 38 or about 104 to about 1042, inclusive of FIG. 170 (SEQ IDNO:252). Preferably, hybridization occurs under stringent hybridizationand wash conditions.

[1434] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209956 (DNA58850-1495), which was deposited on Jun. 9, 1998,or (b) the complement of the DNA molecule of (a).

[1435] In a preferred embodiment, the nucleic acid comprises a DNAmolecule encoding the same mature polypeptide encoded by the humanprotein cDNA in ATCC Deposit No. 209956 (DNA58850-1495).

[1436] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to the sequenceof amino acid residues 1 or about 23 to about 335, inclusive of FIG. 171(SEQ ID NO:253).

[1437] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1138 extracellular domain(ECD), with or without the N-terminal signal sequence and/or theinitiating methionine, and its soluble variants (i.e. transmembranedomain(s) deleted or inactivated) or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 to about amino acidposition 22 in the sequence of FIG. 171 (SEQ ID NO:253). A transmembranedomain region has been tentatively identified as extending from aboutamino acid position 224 to about amino acid position 250 in the PRO1138amino acid sequence (FIG. 171, SEQ ID NO:253).

[1438] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 23 to about 335, inclusive of FIG.171 (SEQ ID NO:253).

[1439] Another embodiment is directed to fragments of a PRO1138polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1440] In another embodiment, the invention provides isolated PRO1138polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1441] In a specific aspect, the invention provides isolated nativesequence PRO1138 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 23 to 335 of FIG. 171 (SEQID NO:253).

[1442] In another aspect, the invention concerns an isolated PRO1138polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to 335, inclusive of FIG. 171 (SEQ ID NO:253).

[1443] In a further aspect, the invention concerns an isolated PRO1138polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 to about 335 of FIG. 171 (SEQ ID NO:253).

[1444] In another aspect, the invention concerns a PRO1138 extracellulardomain comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 to X of FIG. 171 (SEQ ID NO:253), wherein X is any one ofamino acid residues 219 to 228 of FIG. 171 (SEQ ID NO:253).

[1445] In yet another aspect, the invention concerns an isolated PRO1138polypeptide, comprising the sequence of amino acid residues 1 or about23 to about 335, inclusive of FIG. 171 (SEQ ID NO:253), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1138antibody. Preferably, the PRO1138 fragment retains a qualitativebiological activity of a native PRO1138 polypeptide.

[1446] In another aspect, the present invention is directed to fragmentsof a PRO1138 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1447] In yet another embodiment, the invention concerns agonist andantagonists of the PRO1138 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1138 antibody.

[1448] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1138 polypeptide.

[1449] In still a further embodiment, the invention concerns acomposition comprising a PRO1138 polypeptide as hereinabove defined, incombination with a pharmaceutically acceptable carrier.

[1450] In another embodiment, the invention provides a nucleotidesequence designated herein as DNA49140 comprising the nucleotidesequence of FIG. 172 (SEQ ID NO:254).

[1451] 72. PRO1054

[1452] A cDNA clone (DNA58853-1423) has been identified, having homologyto nucleic acid encoding majaor urinary proteins (MUPs) that encodes anovel polypeptide, designated in the present application as “PRO1054”.

[1453] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1054 polypeptide.

[1454] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1054 polypeptide having the sequence of aminoacid residues from about 1 or about 19 to about 180, inclusive of FIG.174 (SEQ ID NO:256), or (b) the complement of the DNA molecule of (a).

[1455] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1054 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 46 orabout 100 and about 585, inclusive, of FIG. 173 (SEQ ID NO:255).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1456] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203016 (DNA58853-1423) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203016 (DNA58853-1423).

[1457] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 19 to about 180, inclusive of FIG. 174(SEQ ID NO:256), or (b) the complement of the DNA of (a).

[1458] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1054 polypeptide having the sequence of amino acidresidues from 1 or about 19 to about 180, inclusive of FIG. 174 (SEQ IDNO:256), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1459] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1054 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 18 in the sequence of FIG.174 (SEQ ID NO:256).

[1460] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256), or (b)the complement of the DNA of (a).

[1461] Another embodiment is directed to fragments of a PRO1054polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 173 (SEQ ID NO:255).

[1462] In another embodiment, the invention provides isolated PRO1054polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1463] In a specific aspect, the invention provides isolated nativesequence PRO1054 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 19 to about 180 ofFIG. 174 (SEQ ID NO:256).

[1464] In another aspect, the invention concerns an isolated PRO1054polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256).

[1465] In a further aspect, the invention concerns an isolated PRO1054polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256).

[1466] In yet another aspect, the invention concerns an isolated PRO1054polypeptide, comprising the sequence of amino acid residues 1 or about19 to about 180, inclusive of FIG. 174 (SEQ ID NO:256), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1054antibody. Preferably, the PRO1054 fragment retains a qualitativebiological activity of a native PRO1054 polypeptide.

[1467] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1054 polypeptide havingthe sequence of amino acid residues from about 1 or about 19 to about180, inclusive of FIG. 174 (SEQ ID NO:256), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1468] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1054 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1054 antibody.

[1469] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1054 polypeptide bycontacting the native PRO1054 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1470] In a still further embodiment, the invention concerns acomposition comprising a PRO1054 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1471] 73. PRO994

[1472] A cDNA clone (DNA58855-1422) has been identified, having homologyto nucleic acid encoding the tumor-associated antigen L6 that encodes anovel polypeptide, designated in the present application as “PRO994”.

[1473] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO994 polypeptide.

[1474] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO994 polypeptide having the sequence of amino acidresidues from about 1 to about 229, inclusive of FIG. 176 (SEQ IDNO:258), or (b) the complement of the DNA molecule of (a).

[1475] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO994 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 31 andabout 717, inclusive, of FIG. 175 (SEQ ID NO:257). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1476] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203018 (DNA58855-1422) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203018 (DNA58855-1422).

[1477] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 to about 229, inclusive of FIG. 176 (SEQ IDNO:258), or (b) the complement of the DNA of (a).

[1478] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO994 polypeptide having the sequence of amino acid residuesfrom 1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, prefereably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1479] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO994 polypeptide, with orwithout the initiating methionine, and its soluble, i.e., transmembranedomain deleted or inactivated variants, or is complementary to suchencoding nucleic acid molecule. The multiple transmembrane domains havebeen tentatively identified as extending from about amino acid position10 to about amino acid position 31, from about amino acid position 50 toabout amino acid position 72, from about amino acid position 87 to aboutamino acid position 110 and from about amino acid position 191 to aboutamino acid position 213 in the PRO994 amino acid sequence (FIG. 176, SEQID NO:258).

[1480] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 229, inclusive of FIG. 176 (SEQ ID NO:258), or (b) thecomplement of the DNA of (a).

[1481] Another embodiment is directed to fragments of a PRO994polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 175 (SEQ ID NO:257).

[1482] In another embodiment, the invention provides isolated PRO994polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1483] In a specific aspect, the invention provides isolated nativesequence PRO994 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 to about 229 of FIG. 176 (SEQID NO:258).

[1484] In another aspect, the invention concerns an isolated PRO994polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 229, inclusive of FIG. 176 (SEQ ID NO:258).

[1485] In a further aspect, the invention concerns an isolated PRO994polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 229, inclusive of FIG. 176 (SEQ ID NO:258).

[1486] In yet another aspect, the invention concerns an isolated PRO994polypeptide, comprising the sequence of amino acid residues 1 to about229, inclusive of FIG. 176 (SEQ ID NO:258), or a fragment thereofsufficient to provide a binding site for an anti-PRO994 antibody.Preferably, the PRO994 fragment retains a qualitative biologicalactivity of a native PRO994 polypeptide.

[1487] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO994 polypeptide havingthe sequence of amino acid residues from about 1 to about 229, inclusiveof FIG. 176 (SEQ ID NO:258), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1488] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO994 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO994 antibody.

[1489] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO994 polypeptide bycontacting the native PRO994 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1490] In a still further embodiment, the invention concerns acomposition comprising a PRO994 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1491] 74. PRO812

[1492] A cDNA clone (DNA59205-1421) has been identified, having homologyto nucleic acid encoding prostatic steroid-binding protein cl thatencodes a novel polypeptide, designated in the present application as“PRO812”.

[1493] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO812 polypeptide.

[1494] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO812 polypeptide having the sequence of amino acidresidues from about 1 or about 16 to about 83, inclusive of FIG. 178(SEQ ID NO:260), or (b) the complement of the DNA molecule of (a).

[1495] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO812 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 55 orabout 100 and about 303, inclusive, of FIG. 177 (SEQ ID NO:259).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1496] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203009 (DNA59205-1421) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203009 (DNA59205-1421).

[1497] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 16 to about 83, inclusive of FIG. 178(SEQ ID NO:260), or (b) the complement of the DNA of (a).

[1498] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 100 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO812 polypeptide having the sequence of aminoacid residues from 1 or about 16 to about 83, inclusive of FIG. 178 (SEQID NO:260), or (b) the complement of the DNA molecule of (a), and, ifthe DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[1499] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO812 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 15 in the sequence of FIG.178 (SEQ ID NO:260).

[1500] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260), or (b)the complement of the DNA of (a).

[1501] Another embodiment is directed to fragments of a PRO812polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 177 (SEQ ID NO:259).

[1502] In another embodiment, the invention provides isolated PRO812polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1503] In a specific aspect, the invention provides isolated nativesequence PRO812 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 16 to about 83 ofFIG. 178 (SEQ ID NO:260).

[1504] In another aspect, the invention concerns an isolated PRO812polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260).

[1505] In a further aspect, the invention concerns an isolated PRO812polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260).

[1506] In yet another aspect, the invention concerns an isolated PRO812polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 83, inclusive of FIG. 178 (SEQ ID NO:260), or a fragmentthereof sufficient to provide a binding site for an anti-PRO812antibody. Preferably, the PRO812 fragment retains a qualitativebiological activity of a native PRO812 polypeptide.

[1507] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO812 polypeptide havingthe sequence of amino acid residues from about 1 or about 16 to about83, inclusive of FIG. 178 (SEQ ID NO:260), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1508] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO812 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO812 antibody.

[1509] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO812 polypeptide bycontacting the native PRO812 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1510] Ina still further embodiment, the invention concerns acomposition comprising a PRO812polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1511] 75. PRO1069

[1512] Applicants have identified a cDNA clone, DNA59211-1450, thatencodes a novel polypeptide having homology to CHIF wherein thepolypeptide is designated in the present application as “PRO1069”.

[1513] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1069 polypeptide.

[1514] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1069 polypeptide having the sequence of aminoacid residues from 1 or about 17 to about 89, inclusive of FIG. 180 (SEQID NO:262), or (b) the complement of the DNA molecule of (a).

[1515] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1069 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid sequence having aboutresidues 197 or about 245 to about 463, inclusive of FIG. 179 (SEQ IDNO:261). Preferably, hybridization occurs under stringent hybridizationand wash conditions.

[1516] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209960 (DNA59211-1450), which was deposited on Jun. 9, 1998.In a preferred embodiment, the nucleic acid comprises a DNA moleculeencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit No. 209960 (DNA59211-1450).

[1517] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 17 to about 89, inclusive of FIG. 180(SEQ ID NO:262).

[1518] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1069 extracellular domain(ECD), with or without the N-terminal signal sequence and/or theinitiating methionine, and its soluble variants (i.e. transmembranedomain(s) deleted or inactivated) or is complementary to such encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 to about amino acidposition 16 in the sequence of FIG. 180 (SEQ ID NO:262). A transmembranedomain region has been tentatively identified as extending from aboutamino acid position 36 to about amino acid position 59 in the PRO1069amino acid sequence (FIG. 180, SEQ ID NO:262).

[1519] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 or about 17 to about 89, inclusive of FIG.180 (SEQ ID NO:262).

[1520] Another embodiment is directed to fragments of a PRO1069polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1521] In another embodiment, the invention provides isolated PRO1069polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1522] In a specific aspect, the invention provides isolated nativesequence PRO1069 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 17 to 89 of FIG. 180 (SEQID NO:262).

[1523] In another aspect, the invention concerns an isolated PRO1069polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 17 to 89, inclusive of FIG. 180 (SEQ ID NO:262).

[1524] In a further aspect, the invention concerns an isolated PRO1069polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 17 to about 89 of FIG. 180 (SEQ ID NO:262).

[1525] In another aspect, the invention concerns a PRO1069 extracellulardomain comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 17 to X of FIG. 180 (SEQ ID NO:262), wherein X is any one ofamino acid residues 32 to 41 of FIG. 180 (SEQ ID NO:262).

[1526] In yet another aspect, the invention concerns an isolated PRO1069polypeptide, comprising the sequence of amino acid residues 1 or about17 to about 89, inclusive of FIG. 180 (SEQ ID NO:262), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1069antibody. Preferably, the PRO1069 fragment retains a qualitativebiological activity of a native PRO1069 polypeptide.

[1527] In another aspect, the present invention is directed to fragmentsof a PRO1069 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1528] In yet another embodiment, the invention concerns agonist andantagonists of the PRO1069 polypeptide. In a particular embodiment, theagonist or antagonist is an anti-PRO1069 antibody.

[1529] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1069 polypeptide.

[1530] In still a further embodiment, the invention concerns acomposition comprising a PRO1069 polypeptide as hereinabove defined, incombination with a pharmaceutically acceptable carrier.

[1531] 76. PRO1129

[1532] Applicants have identified a cDNA clone (DNA59213-1487) havinghomology to nucleic acid encoding cytochrome P-450 family members thatencodes a novel polypeptide, designated in the present application as“PRO1129”.

[1533] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1129 polypeptide.

[1534] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1129 polypeptide having the sequence of aminoacid residues from about 1 to about 524, inclusive of FIG. 182 (SEQ IDNO:264), or (b) the complement of the DNA molecule of (a).

[1535] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1129 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 42 andabout 1613, inclusive, of FIG. 181 (SEQ ID NO:263). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1536] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209959 (DNA59213-1487). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209959(DNA59213-1487).

[1537] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 to about 524, inclusive of FIG. 182 (SEQ IDNO:264).

[1538] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1129 polypeptide, with orwithout the initiating methionine, and its soluble, i.e., transmembranedomain deleted or inactivated variants, or is complementary to suchencoding nucleic acid molecule. The type II transmembrane domains havebeen tentatively identified as extending from about amino acid position13 to about amino acid position 32 and from about amino acid position 77to about amino acid position 102 in the PRO1129 amino acid sequence(FIG. 182, SEQ ID NO:264).

[1539] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 524, inclusive of FIG. 182 (SEQ ID NO:264).

[1540] Another embodiment is directed to fragments of a PRO1129polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1541] In another embodiment, the invention provides isolated PRO1129polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1542] In a specific aspect, the invention provides isolated nativesequence PRO1129 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to about 524 of FIG. 182 (SEQ IDNO:264).

[1543] In another aspect, the invention concerns an isolated PRO1129polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 524, inclusive of FIG. 182 (SEQ ID NO:264).

[1544] In a further aspect, the invention concerns an isolated PRO1129polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 524, inclusive of FIG. 182 (SEQ ID NO:264).

[1545] In yet another aspect, the invention concerns an isolated PRO1129polypeptide, comprising the sequence of amino acid residues 1 to about524, inclusive of FIG. 182 (SEQ ID NO:264), or a fragment thereofsufficient to provide a binding site for an anti-PRO1129 antibody.Preferably, the PRO1129 fragment retains a qualitative biologicalactivity of a native PRO1129 polypeptide.

[1546] In another aspect, the present invention is directed to fragmentsof a PRO1129 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1547] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1129 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1129 antibody.

[1548] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1129 polypeptide.

[1549] In still a further embodiment, the invention concerns acomposition comprising a PRO1129 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1550] 77. PRO1068

[1551] A cDNA clone (DNA59214-1449) has been identified, that encodes anovel polypeptide having homology to urotensin and designated thepresent application as “PRO1068.”

[1552] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1068 polypeptide.

[1553] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1068 polypeptide having the sequence of aminoacid residues from about 21 to about 124, inclusive of FIG. 184 (SEQ IDNO:266), or (b) the complement of the DNA molecule of (a).

[1554] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1068 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 102 andabout 413, inclusive, of FIG. 183 (SEQ ID NO:265). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1555] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203046 (DNA59214-1449), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203046 (DNA59214-1449).

[1556] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 21 to about 124, inclusive of FIG. 184(SEQ ID NO:266), or the complement of the DNA of (a).

[1557] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1068 polypeptide having the sequence of amino acid residues fromabout 21 to about 124, inclusive of FIG. 184 (SEQ ID NO:266), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1558] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1068 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 20 in the sequence of FIG.184 (SEQ ID NO:266).

[1559] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 21to about 124, inclusive of FIG. 184 (SEQ ID NO:266), or (b) thecomplement of the DNA of (a).

[1560] Another embodiment is directed to fragments of a PRO1068polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1561] In another embodiment, the invention provides isolated PRO1068polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1562] In a specific aspect, the invention provides isolated nativesequence PRO1068 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 21 to 124 of FIG. 184 (SEQ ID NO:266).

[1563] In another aspect, the invention concerns an isolated PRO1068polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues21 to about 124, inclusive of FIG. 184 (SEQ ID NO:266).

[1564] In a further aspect, the invention concerns an isolated PRO1068polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 21 to124 of FIG. 184 (SEQ ID NO:266).

[1565] In yet another aspect, the invention concerns an isolated PRO1068polypeptide, comprising the sequence of amino acid residues 21 to about124, inclusive of FIG. 184 (SEQ ID NO:266), or a fragment thereofsufficient to provide a binding site for an anti-PRO1068 antibody.Preferably, the PRO1068 fragment retains a qualitative biologicalactivity of a native PRO1068 polypeptide.

[1566] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1068 polypeptide havingthe sequence of amino acid residues from about 21 to about 124,inclusive of FIG. 184 (SEQ ID NO:266), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1567] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1068 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1068 antibody.

[1568] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1068 polypeptide, bycontacting the native PRO1068 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1569] In a still further embodiment, the invention concerns acomposition comprising a PRO1068 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1570] 78. PRO1066

[1571] Applicants have identified a cDNA clone (DNA59215-1425) thatencodes a novel secreted polypeptide, designated in the presentapplication as “PRO1066”.

[1572] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1066 polypeptide.

[1573] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1066 polypeptide having the sequence of aminoacid residues from about 1 or about 24 to about 117, inclusive of FIG.186 (SEQ ID NO:268), or (b) the complement of the DNA molecule of (a).

[1574] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1066 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 176 orabout 245 and about 527, inclusive, of FIG. 185 (SEQ ID NO:267).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1575] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209961 (DNA59215-1425). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209961(DNA59215-1425).

[1576] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 24 to about 117, inclusive of FIG. 186(SEQ ID NO:268).

[1577] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1066 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 23 in the sequence of FIG.186 (SEQ ID NO:268).

[1578] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

[1579] Another embodiment is directed to fragments of a PRO1066polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1580] In another embodiment, the invention provides isolated PRO1066polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1581] In a specific aspect, the invention provides isolated nativesequence PRO1066 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 24 to about 117 of FIG. 186(SEQ ID NO:268).

[1582] In another aspect, the invention concerns an isolated PRO1066polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

[1583] In a further aspect, the invention concerns an isolated PRO1066polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268).

[1584] In yet another aspect, the invention concerns an isolated PRO1066polypeptide, comprising the sequence of amino acid residues 1 or about24 to about 117, inclusive of FIG. 186 (SEQ ID NO:268), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1066antibody. Preferably, the PRO1066 fragment retains a qualitativebiological activity of a native PRO1066 polypeptide.

[1585] In another aspect, the present invention is directed to fragmentsof a PRO1066 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1586] 79. PRO1184

[1587] Applicants have identified a cDNA clone (DNA59220-1514) thatencodes a novel secreted polypeptide, designated in the presentapplication as “PRO1184”.

[1588] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1184 polypeptide.

[1589] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1184 polypeptide having the sequence of aminoacid residues from 1 or about 39 through 142 of FIG. 188 (SEQ IDNO:270), or (b) the complement of the DNA molecule of (a).

[1590] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1184 polypeptide comprising DNA hybridizingto the complement of the nucleic acid at about residues 106 or 220through 531 of SEQ ID NO:269. In another aspect, the invention concernsan isolated nucleic acid molecule encoding a PRO1184 polypeptidecomprising DNA hybridizing to the complement of the nucleic of SEQ IDNO:269. Preferably, hybridization occurs under stringent hybridizationand wash conditions.

[1591] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCC ofDNA59220-1514.

[1592] In a preferred embodiment, the nucleic acid comprises a DNAencoding the same mature polypeptide encoded by the human protein cDNAin ATCC Deposit of DNA59220-1514.

[1593] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 39 through 142 of SEQ ID NO:270.

[1594] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1184 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble variants, or is complementary to such an encodingnucleic acid molecule. The signal peptide has been tentativelyidentified as extending from amino acid position 1 to about amino acidposition 38 of SEQ ID NO:270.

[1595] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 39 through 142 of SEQ ID NO:270.

[1596] Another embodiment is directed to fragments of a PRO1184polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length.

[1597] In another embodiment, the invention provides isolated PRO1184polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1598] In a specific aspect, the invention provides isolated nativesequence PRO1184 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 39 through 142 of SEQ IDNO:270.

[1599] In another aspect, the invention concerns an isolated PRO1184polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 39 through 142 of SEQ ID NO:270.

[1600] In a further aspect, the invention concerns an isolated PRO1184polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 39 through 142 of SEQ ID NO:270.

[1601] In yet another aspect, the invention concerns an isolated PRO1184polypeptide, comprising the sequence of amino acid residues 1 or about39 through 142 of SEQ ID NO:270, or a fragment thereof sufficient toprovide a binding site for an anti-PRO1184 antibody. Preferably, thePRO1184 fragment retains a qualitative biological activity of a nativePRO1184 polypeptide.

[1602] In another aspect, the present invention is directed to fragmentsof a PRO1184 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated.

[1603] 80. PRO1360

[1604] A cDNA clone (DNA59488-1603) has been identified that encodes anovel polypeptide designated in the present application as “PRO1360.”

[1605] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1360 polypeptide.

[1606] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1360 polypeptide having the sequence of aminoacid residues from about 30 to about 285, inclusive of FIG. 190 (SEQ IDNO:272), or (b) the complement of the DNA molecule of (a).

[1607] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1360 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 140 andabout 908, inclusive, of FIG. 189 (SEQ ID NO:271). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1608] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203157 (DNA59488-1603), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203157 (DNA59488-1603).

[1609] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 30 to about 285, inclusive of FIG. 190(SEQ ID NO:272), or the complement of the DNA of (a).

[1610] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1360 polypeptide having the sequence of amino acid residues fromabout 30 to about 285, inclusive of FIG. 190 (SEQ ID NO:272), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1611] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 30to about 285, inclusive of FIG. 190 (SEQ ID NO:272), or (b) thecomplement of the DNA of (a).

[1612] Another embodiment is directed to fragments of a PRO1360polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1613] In another embodiment, the invention provides isolated PRO1360polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1614] In a specific aspect, the invention provides isolated nativesequence PRO1360 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 30 through 285 of FIG. 190 (SEQ IDNO:272).

[1615] In another aspect, the invention concerns an isolated PRO1360polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues30 to about 285, inclusive of FIG. 190 (SEQ ID NO:272).

[1616] In a further aspect, the invention concerns an isolated PRO1360polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 30through 285 of FIG. 190 (SEQ ID NO:272).

[1617] In yet another aspect, the invention concerns an isolated PRO1360polypeptide, comprising the sequence of amino acid residues 30 to about285, inclusive of FIG. 190 (SEQ ID NO:272), or a fragment thereofsufficient to provide a binding site for an anti-PRO1360 antibody.Preferably, the PRO1360 fragment retains a qualitative biologicalactivity of a native PRO1360 polypeptide.

[1618] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1360 polypeptide havingthe sequence of amino acid residues from about 30 to about 285,inclusive of FIG. 190 (SEQ ID NO:272), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1619] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1360 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1360 antibody.

[1620] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1360 polypeptide, bycontacting the native PRO1360 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1621] In a still further embodiment, the invention concerns acomposition comprising a PRO1360 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1622] 81. PRO1029

[1623] A cDNA clone (DNA59493-1420) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1029”.

[1624] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1029 polypeptide.

[1625] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1029 polypeptide having the sequence of aminoacid residues from about 1 or about 20 to about 86, inclusive of FIG.192 (SEQ ID NO:274), or (b) the complement of the DNA molecule of (a).

[1626] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1029 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 39 orabout 96 and about 296, inclusive, of FIG. 191 (SEQ ID NO:274).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1627] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203050 (DNA59493-1420) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203050 (DNA59493-1420).

[1628] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 20 to about 86, inclusive of FIG. 192(SEQ ID NO:274), or (b) the complement of the DNA of (a).

[1629] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1029 polypeptide having the sequence of amino acidresidues from 1 or about 20 to about 86, inclusive of FIG. 192 (SEQ IDNO:274), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1630] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1029 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 19 in the sequence of FIG.192 (SEQ ID NO:274).

[1631] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274), or (b)the complement of the DNA of (a).

[1632] Another embodiment is directed to fragments of a PRO1029polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 191 (SEQ ID NO:273).

[1633] In another embodiment, the invention provides isolated PRO1029polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1634] In a specific aspect, the invention provides isolated nativesequence PRO1029 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 20 to about 86 ofFIG. 192 (SEQ ID NO:274).

[1635] In another aspect, the invention concerns an isolated PRO1029polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274).

[1636] In a further aspect, the invention concerns an isolated PRO1029polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274).

[1637] In yet another aspect, the invention concerns an isolated PRO1029polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 86, inclusive of FIG. 192 (SEQ ID NO:274), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1029antibody. Preferably, the PRO1029 fragment retains a qualitativebiological activity of a native PRO1029 polypeptide.

[1638] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1029 polypeptide havingthe sequence of amino acid residues from about 1 or about 20 to about86, inclusive of FIG. 192 (SEQ ID NO:274), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1639] 82. PRO1139

[1640] Applicants have identified a novel cDNA clone (DNA59497-1496)that encodes a novel human protein originally designated as PRO1139.

[1641] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding aPRO1139 polypeptide having the sequence of amino acid residues fromabout 29 to about 131 of FIG. 194 (SEQ ID NO:276), or (b) the complementof the DNA molecule of (a).

[1642] In another embodiment, the invention concerns an isolated nucleicacid molecule comprising DNA hybridizing to the complement of thepolynucleotide sequence between about residues 80 and 391, inclusive, ofFIG. 193 (SEQ ID NO:275). Preferably, hybridization occurs understringent hybridization and wash conditions.

[1643] In a further embodiment, the invention concerns an isolatednucleic acid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209941 (DNA59497-1496). In a preferred embodiment, thenucleic acid comprises a DNA encoding the same mature polypeptideencoded by the human protein cDNA in ATCC Deposit No. 209941(DNA59497-1496).

[1644] In a still further embodiment, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 29 to about 131 of FIG. 194 (SEQ IDNO:276).

[1645] In a specific embodiment, the invention provides an isolatednucleic acid molecule comprising DNA encoding a native or variantPRO1139 polypeptide, with or without the N-terminal signal sequence, andwith or without the transmembrane regions which have been identified asstretching from about amino acid position 33 to about amino acidposition 52; from about amino acid position 71 to about amino acidposition 89; and from about amino acid position 98 to about amino acidposition 120, respectively of the amino acid sequence of FIG. 194, SEQID NO:276. In one aspect, the isolated nucleic acid comprises DNAencoding a mature, full-length native PRO1139 polypeptide having aminoacid residues 1 to 131 of FIG. 194, SEQ ID NO:276, or is complementaryto such encoding nucleic acid sequence.

[1646] In another embodiment, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residuesfrom about 29 to about 131 of FIG. 194 (SEQ ID NO:276).

[1647] In another embodiment, the invention provides isolated PRO1139polypeptides. In particular, the invention provides isolated nativesequence PRO1139 polypeptide, which in one embodiment, include the aminoacid sequence comprising residues 29 to 131 of FIG. 194 (SEQ ID NO:276).The invention also provides for variants of the PRO1139 polypeptidewhich are encoded by any of the isolated nucleic acid moleculeshereinabove defined. Specific variants include, but are not limited to,deletion (truncated) variants of the full-length native sequence PRO1139which lack the N-terminal signal sequence and/or have at least onetransmembrane domain deleted or inactivated. The variants specificallyinclude variants of the full-length mature polypeptide of FIG. 194 (SEQID NO:276) in which one or more of the transmembrane regions betweenamino acid residues 33-52, 71-8, and 98-120, respectively have beendeleted or inactivated, and which may additionally have the N-terminalsignal sequence (amino acid residues 1-28) and/or the initiatingmethionine deleted.

[1648] In a further embodiment, the invention concerns an isolatedPRO1139 polypeptide, comprising an amino acid sequence scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residuesfrom about 29 to about 131 of FIG. 194 (SEQ ID NO:276).

[1649] In yet another aspect, the invention concerns an isolated PRO1139polypeptide, comprising the sequence of amino acid residues 29 to about131, inclusive of FIG. 194 (SEQ ID NO:276) or a fragment thereofsufficient to provide a binding site for an anti-PRO1139 antibody.Preferably, the PRO1139 fragment retains a qualitative biologicalactivity of a native PRO1139 polypeptide.

[1650] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1139 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1139 antibody.

[1651] In a further embodiment, the invention concerns screening assaysto identify agonists or antagonists of a native PRO1139 polypeptide.

[1652] In a still further embodiment, the invention concerns acomposition comprising a PRO1139 polypeptide (including variants), or anagonist or antagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1653] The invention also concerns a method of treating obesitycomprising administering to a patient an effective amount of anantagonist of a PRO139 polypeptide. In a specific embodiment, theantagonist is a blocking antibody specifically binding a native PRO1139polypeptide.

[1654] 83. PRO1309

[1655] A cDNA clone (DNA59588-1571) has been identified that encodes anovel polypeptide having leucine rich repeats and designated in thepresent application as “PRO1309.”

[1656] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1309 polypeptide.

[1657] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1309 polypeptide having the sequence of aminoacid residues from about 35 to about 522, inclusive of FIG. 196 (SEQ IDNO:278), or (b) the complement of the DNA molecule of (a).

[1658] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1309 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 822 andabout 2285, inclusive, of FIG. 195 (SEQ ID NO:277). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1659] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203106 (DNA59588-1571), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203106 (DNA59588-1571).

[1660] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 35 to about 522, inclusive of FIG. 196(SEQ ID NO:278), or the complement of the DNA of (a).

[1661] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1309 polypeptide having the sequence of amino acid residues fromabout 35 to about 522, inclusive of FIG. 196 (SEQ ID NO:278), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1662] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1309 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 34 in thesequence of FIG. 196 (SEQ ID NO:278). The transmembrane domain has beententatively identified as extending from about amino acid position 428through about amino acid position 450 in the PRO1309 amino acid sequence(FIG. 196, SEQ ID NO:278).

[1663] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 35to about 522, inclusive of FIG. 196 (SEQ ID NO:278), or (b) thecomplement of the DNA of (a).

[1664] Another embodiment is directed to fragments of a PRO1309polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1665] In another embodiment, the invention provides isolated PRO1309polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1666] In a specific aspect, the invention provides isolated nativesequence PRO1309 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 35 through 522 of FIG. 196 (SEQ IDNO:278).

[1667] In another aspect, the invention concerns an isolated PRO1309polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues35 to about 522, inclusive of FIG. 196 (SEQ ID NO:278).

[1668] In a further aspect, the invention concerns an isolated PRO1309polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 35through 522 of FIG. 196 (SEQ ID NO:278).

[1669] In yet another aspect, the invention concerns an isolated PRO1309polypeptide, comprising the sequence of amino acid residues 35 to about522, inclusive of FIG. 196 (SEQ ID NO:278), or a fragment thereofsufficient to provide a binding site for an anti-PRO1309 antibody.Preferably, the PRO1309 fragment retains a qualitative biologicalactivity of a native PRO1309 polypeptide.

[1670] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1309 polypeptide havingthe sequence of amino acid residues from about 35 to about 522,inclusive of FIG. 196 (SEQ ID NO:278), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1671] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1309 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1309 antibody.

[1672] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1309 polypeptide, bycontacting the native PRO1309 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1673] In a still further embodiment, the invention concerns acomposition comprising a PRO1309 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1674] 84. PRO1028

[1675] Applicants have identified a cDNA clone that encodes a secretednovel polypeptide, wherein the polypeptide is designated in the presentapplication as “PRO1028”.

[1676] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1028 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1028polypeptide having amino acid residues 1 through 197 of FIG. 198 (SEQ IDNO:281), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. The isolated nucleic acid sequence maycomprise the cDNA insert of the vector deposited on Jun. 9, 1998 withthe ATCC as DNA59603-1419 which includes the nucleotide sequenceencoding PRO1028.

[1677] In another embodiment, the invention provides isolated PRO1028polypeptide. In particular, the invention provides isolated nativesequence PRO1028 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 197 of FIG. 198 (SEQ IDNO:281). Optionally, the PRO1028 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe vector deposited on Jun. 9, 1998 with the ATCC as DNA59603-1419.

[1678] 85. PRO1027

[1679] A cDNA clone (DNA59605-1418) has been identified, having a typeII fibronectin collagen-binding domain that encodes a novel polypeptide,designated in the present application as “PRO1027.”

[1680] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1027 polypeptide.

[1681] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1027 polypeptide having the sequence of aminoacid residues from about 1 or 34 to about 77, inclusive of FIG. 200 (SEQID NO:283), or (b) the complement of the DNA molecule of (a). The term“or” as used herein to refer to amino or nucleic acids is meant to referto two alternative embodiments provided herein, i.e., 1-77, or inanother embodiment, 34-77.

[1682] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1027 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 31 or 130and about 261, inclusive, of FIG. 199 (SEQ ID NO:282). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1683] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203005 (DNA59605-1418), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203005 (DNA59605-1418).

[1684] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 34 to about 77, inclusive of FIG.200 (SEQ ID NO:283), or the complement of the DNA of (a).

[1685] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1027polypeptide having the sequence of amino acid residues from about 1 or34 to about 77, inclusive of FIG. 200 (SEQ ID NO:283), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1686] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 34 to about 77, inclusive of FIG. 200 (SEQ ID NO:283), or (b) thecomplement of the DNA of (a).

[1687] In another embodiment, the invention provides isolated PRO1027polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1688] In a specific aspect, the invention provides isolated nativesequence PRO1027 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 34 through 77 of FIG. 200 (SEQ IDNO:283).

[1689] In another aspect, the invention concerns an isolated PRO1027polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 34 to about 77, inclusive of FIG. 200 (SEQ ID NO:283).

[1690] In a further aspect, the invention concerns an isolated PRO1027polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 34through 77 of FIG. 200 (SEQ ID NO:283).

[1691] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1027 polypeptide havingthe sequence of amino acid residues from about 1 or 34 to about 77,inclusive of FIG. 200 (SEQ ID NO:283), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1692] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1027 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1027 antibody.

[1693] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1027 polypeptide, bycontacting the native PRO1027 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1694] In a still further embodiment, the invention concerns acomposition comprising a PRO1027 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1695] 86. PRO1107

[1696] Applicants have identified a cDNA clone that encodes a novelpolypeptide having sequence identity with PC-1, wherein the polypeptideis designated in the present application as “PRO1107”.

[1697] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1107 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1107polypeptide having amino acid residues 1 through 477 of FIG. 202 (SEQ IDNO:285), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO1107 polypeptide having amino acidresidues about 23 through 477 of FIG. 202 (SEQ ID NO:285) or amino acidsabout 1 or 23 through 428±5 of FIG. 202 (SEQ ID NO:285), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA59606-1471 vector deposited on Jun. 9, 1998with the ATCC, which includes the nucleotide sequence encoding PRO1107.

[1698] In another embodiment, the invention provides isolated PRO1107polypeptide. In particular, the invention provides isolated nativesequence PRO1107 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 477 of FIG. 202 (SEQ IDNO:285). Additional embodiments of the present invention are directed toPRO1107 polypeptides comprising amino acids about 23 through 477 of FIG.202 (SEQ ID NO:285) or amino acids about 1 or 23 through 428±5 of FIG.202 (SEQ ID NO:285). Optionally, the PRO1107 polypeptide is obtained oris obtainable by expressing the polypeptide encoded by the cDNA insertof the DNA59606-1471 vector deposited with the ATCC on Jun. 9, 1998.

[1699] 87. PRO1140

[1700] Applicants have identified a cDNA clone, DNA59607-1497, thatencodes a novel multi-span transmembrane polypeptide wherein thepolypeptide is designated in the present application as “PRO1140”.

[1701] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1140 polypeptide.

[1702] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1140 polypeptide having the sequence of aminoacid residues from 1 to about 255, inclusive of FIG. 204 (SEQ IDNO:287), or (b) the complement of the DNA molecule of (a).

[1703] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1140 polypeptide comprising DNA thathybridizes to the complement of the nucleic acid sequence having aboutresidues 210 to about 974, inclusive of FIG. 203 (SEQ ID NO:286).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1704] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209946 (DNA59607-1497), which was deposited on Jun. 9, 1998,or (b) the complement of the DNA molecule of (a). In a preferredembodiment, the nucleic acid comprises a DNA molecule encoding the samemature polypeptide encoded by the human protein cDNA in ATCC Deposit No.209946 (DNA59607-1497).

[1705] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising DNA encoding a polypeptide having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,and most preferably at least about 95% sequence identity to the sequenceof amino acid residues 1 to about 255, inclusive of FIG. 204 (SEQ IDNO:287).

[1706] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1140 extracellular domain(ECD), with or without the initiating methionine, and its solublevariants (i.e. transmembrane domain(s) deleted or inactivated) or iscomplementary to such encoding nucleic acid molecule. Referring to thePRO1140 amino acid sequence (SEQ ID NO:287) shown in FIG. 204,transmembrane domain regions have been tentatively identified asextending from about amino acid positions 101 to about 118, about 141 toabout 161, and from about 172 to about 191.

[1707] In another aspect, the invention concerns an isolated nucleicacid molecule comprising DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 90% positives, and mostpreferably at least about 95% positives when compared with the aminoacid sequence of residues 1 to about 255, inclusive of FIG. 204 (SEQ IDNO:287).

[1708] Another embodiment is directed to fragments of a PRO1140polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1709] In another embodiment, the invention provides isolated PRO1140polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1710] In a specific aspect, the invention provides isolated nativesequence PRO1140 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 255 of FIG. 204 (SEQ ID NO:287).

[1711] In another aspect, the invention concerns an isolated PRO1140polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to 255, inclusive of FIG. 204 (SEQ ID NO:287).

[1712] In a further aspect, the invention concerns an isolated PRO1140polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, and most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 toabout 255 of FIG. 204 (SEQ ID NO:287).

[1713] In another aspect, the invention concerns a PRO1140 extracellulardomain comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, and most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to X of FIG. 204 (SEQ ID NO:287), wherein X is any one of amino acidresidues 96 to 105 of FIG. 204 (SEQ ID NO:287).

[1714] In yet another aspect, the invention concerns an isolated PRO1140polypeptide, comprising the sequence of amino acid residues 1 to about255, inclusive of FIG. 204 (SEQ ID NO:287), or a fragment thereofsufficient to provide a binding site for an anti-PRO1140 antibody.Preferably, the PRO1140 fragment retains a qualitative biologicalactivity of a native PRO1140 polypeptide.

[1715] In another aspect, the present invention is directed to fragmentsof a PRO1140 polypeptide which are sufficiently long to provide anepitope against which an antibody may be generated. 88. PRO1106

[1716] Applicants have identified a cDNA clone that encodes a novelpolypeptide having sequence identity with a peroxisomalcalcium-dependent solute carrier, wherein the polypeptide is designatedin the present application as “PRO1106”.

[1717] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1106 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1106polypeptide having amino acid residues 1 through 469 of FIG. 206 (SEQ IDNO:289), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. The isolated nucleic acid sequence maycomprise the cDNA insert of the DNA59609-1470 vector deposited on Jun.9, 1998 with the ATCC, which includes the nucleotide sequence encodingPRO1106.

[1718] In another embodiment, the invention provides isolated PRO1106polypeptide. In particular, the invention provides isolated nativesequence PRO1106 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 469 of FIG. 206 (SEQ IDNO:289). Optionally, the PRO1106 polypeptide is obtained or isobtainable by expressing the polypeptide encoded by the cDNA insert ofthe DNA59609-1470 vector deposited with the ATCC on Jun. 9, 1998.

[1719] 89. PRO1291

[1720] A cDNA clone (DNA59610-1556) has been identified, having homologyto nucleic acid encoding butyrophilin that encodes a novel polypeptide,designated in the present application as “PRO1291”.

[1721] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1291 polypeptide.

[1722] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1291 polypeptide having the sequence of aminoacid residues from about 1 or about 29 to about 282, inclusive of FIG.208 (SEQ ID NO:291), or (b) the complement of the DNA molecule of (a).

[1723] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1291 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 61 orabout 145 and about 906, inclusive, of FIG. 207 (SEQ ID NO:290).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1724] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209990 (DNA59610-1556) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209990 (DNA59610-1556).

[1725] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 29 to about 282, inclusive of FIG. 208(SEQ ID NO:291), or (b) the complement of the DNA of (a).

[1726] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1291 polypeptide having the sequence of amino acidresidues from 1 or about 29 to about 282, inclusive of FIG. 208 (SEQ IDNO:291), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1727] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1291 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 28 in thesequence of FIG. 208 (SEQ ID NO:291). The transmembrane domain has beententatively identified as extending from about amino acid position 258to about amino acid position 281 in the PRO1291 amino acid sequence(FIG. 208, SEQ ID NO:291).

[1728] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291), or (b)the complement of the DNA of (a).

[1729] Another embodiment is directed to fragments of a PRO1291polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 207 (SEQ ID NO:290).

[1730] In another embodiment, the invention provides isolated PRO1291polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1731] In a specific aspect, the invention provides isolated nativesequence PRO1291 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 29 to about 282 ofFIG. 208 (SEQ ID NO:291).

[1732] In another aspect, the invention concerns an isolated PRO1291polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291).

[1733] In a further aspect, the invention concerns an isolated PRO1291polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291).

[1734] In yet another aspect, the invention concerns an isolated PRO1291polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 282, inclusive of FIG. 208 (SEQ ID NO:291), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1291antibody. Preferably, the PRO1291 fragment retains a qualitativebiological activity of a native PRO1291 polypeptide.

[1735] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1291 polypeptide havingthe sequence of amino acid residues from about 1 or about 29 to about282, inclusive of FIG. 208 (SEQ ID NO:291), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1736] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1291 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1291 antibody.

[1737] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1291 polypeptide bycontacting the native PRO1291 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1738] In a still further embodiment, the invention concerns acomposition comprising a PRO1291 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1739] 90. PRO1105

[1740] Applicants have identified a cDNA clone that encodes a novelpolypeptide having two transmembrane domains, wherein the polypeptide isdesignated in the present application as “PRO1105”.

[1741] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1105 polypeptide. In oneaspect, the isolated nucleic acid comprises DNA encoding the PRO1105polypeptide having amino acid residues 1 through 180 of FIG. 210 (SEQ IDNO:293), or is complementary to such encoding nucleic acid sequence, andremains stably bound to it under at least moderate, and optionally,under high stringency conditions. In other aspects, the isolated nucleicacid comprises DNA encoding the PRO1105 polypeptide having amino acidresidues about 20 through 180 of FIG. 210 (SEQ ID NO:293), or iscomplementary to such encoding nucleic acid sequence, and remains stablybound to it under at least moderate, and optionally, under highstringency conditions. The isolated nucleic acid sequence may comprisethe cDNA insert of the DNA59612-1466 vector deposited on Jun. 9, 1998with the ATCC, which includes the nucleotide sequence encoding PRO1105.

[1742] In another embodiment, the invention provides isolated PRO1105polypeptide. In particular, the invention provides isolated nativesequence PRO1105 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 180 of FIG. 210 (SEQ IDNO:293). Additional embodiments of the present invention are directed toPRO1105 polypeptides comprising amino acids about 20 through 180 of FIG.210 (SEQ ID NO:293). Other embodiments of the present invention aredirected to PRO1105 polypeptides comprising amino acids about 1 through79 and 100 through about 144 of FIG. 210 (SEQ ID NO:293). Optionally,the PRO1105 polypeptide is obtained or is obtainable by expressing thepolypeptide encoded by the cDNA insert of the DNA59612-1466 vectordeposited with the ATCC on Jun. 9, 1998.

[1743] 91. PRO511

[1744] A cDNA clone (DNA59613-1417) has been identified, having somesequence identity with RoBo-1 and phospholipase inhibitors that encodesa novel polypeptide, designated in the present application as “PRO1026.”

[1745] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1026 polypeptide.

[1746] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1026 polypeptide having the sequence of aminoacid residues from about 1 or 26 to about 237, inclusive of FIG. 212(SEQ ID NO:295), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to amino or nucleic acids is meant torefer to two alternative embodiments provided herein, i.e., 1-237, or inanother embodiment, 26-237.

[1747] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1026 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 233 or 308and about 943, inclusive, of FIG. 212 (SEQ ID NO:295). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1748] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203007 (DNA59613-1417), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203007 (DNA59613-1417).

[1749] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 26 to about 237, inclusive of FIG.212 (SEQ ID NO:295), or the complement of the DNA of (a).

[1750] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1026polypeptide having the sequence of amino acid residues from about 1 or26 to about 237, inclusive of FIG. 212 (SEQ ID NO:295), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1751] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 237, inclusive of FIG. 212 (SEQ ID NO:295), or (b) thecomplement of the DNA of (a).

[1752] In another embodiment, the invention provides isolated PRO1026polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1753] In a specific aspect, the invention provides isolated nativesequence PRO1026 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 26 through 237 of FIG. 212 (SEQID NO:295).

[1754] In another aspect, the invention concerns an isolated PRO1026polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 237, inclusive of FIG. 212 (SEQ ID NO:295).

[1755] In a further aspect, the invention concerns an isolated PRO1026polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 237 of FIG. 212 (SEQ ID NO:295).

[1756] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1026 polypeptide havingthe sequence of amino acid residues from about 1 or 26 to about 237,inclusive of FIG. 212 (SEQ ID NO:295), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1757] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1026 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1026 antibody.

[1758] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1026 polypeptide, bycontacting the native PRO1026 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1759] In a still further embodiment, the invention concerns acomposition comprising a PRO1026 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1760] 92. PRO1104

[1761] A cDNA clone (DNA59616-1465) has been identified, that encodes anovel polypeptide, designated in the present application as “PRO1104.”

[1762] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1104 polypeptide.

[1763] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1104 polypeptide having the sequence of aminoacid residues from about 1 or about 23 to about 341, inclusive of FIG.214 (SEQ ID NO:297), or (b) the complement of the DNA molecule of (a).The term “or” as used herein to refer to amino or nucleic acids is meantto refer to two alternative embodiments provided herein, i.e., 1-341, orin another embodiment, 23-341.

[1764] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1104 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 109 or 175and about 1131, inclusive, of FIG. 213 (SEQ ID NO:296). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1765] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209991 (DNA59616-1465), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209991 (DNA59616-1465).

[1766] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or about 23 to about 341, inclusive ofFIG. 214 (SEQ ID NO:297), or the complement of the DNA of (a).

[1767] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1104polypeptide having the sequence of amino acid residues from about 1 orabout 23 to about 341, inclusive of FIG. 214 (SEQ ID NO:297), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1768] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 23 to about 341, inclusive of FIG. 214 (SEQ ID NO:297), or (b)the complement of the DNA of (a).

[1769] In another embodiment, the invention provides isolated PRO1104polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1770] In a specific aspect, the invention provides isolated nativesequence PRO1104 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or about 23 through 341 of FIG. 214(SEQ ID NO:297).

[1771] In another aspect, the invention concerns an isolated PRO1104polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 23 through about 341, inclusive of FIG. 214 (SEQ ID NO:297).

[1772] In a further aspect, the invention concerns an isolated PRO1104polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 23 through 341 of FIG. 214 (SEQ ID NO:297).

[1773] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1104 polypeptide havingthe sequence of amino acid residues from about 1 or about 23 to about341, inclusive of FIG. 214 (SEQ ID NO:297), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1774] 93. PRO1100

[1775] A cDNA clone (DNA59619-1464) has been identified that encodes anovel polypeptide having multiple transmembrane domains, designated inthe present application as “PRO1100.”

[1776] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1100 polypeptide.

[1777] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1100 polypeptide having the sequence of aminoacid residues from about 1 or 21 to about 320, inclusive of FIG. 216(SEQ ID NO:299), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to amino or nucleic acids is meant torefer to two alternative embodiments provided herein, i.e., 1-320, or inanother embodiment, 21-320.

[1778] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1100 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 33 or 93and about 992, inclusive, of FIG. 215 (SEQ ID NO:298). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1779] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203041 (DNA59619-1464), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203041 (DNA59619-1464).

[1780] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 21 to about 320, inclusive of FIG.216 (SEQ ID NO:299), or the complement of the DNA of (a).

[1781] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1100polypeptide having the sequence of amino acid residues from about 1 or21 to about 320, inclusive of FIG. 216 (SEQ ID NO:299), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1782] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1100 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domains deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.

[1783] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 320, inclusive of FIG. 216 (SEQ ID NO:299), or (b) thecomplement of the DNA of (a).

[1784] In another embodiment, the invention provides isolated PRO1100polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1785] In a specific aspect, the invention provides isolated nativesequence PRO1100 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 21 through 320 of FIG. 216 (SEQID NO:299).

[1786] In another aspect, the invention concerns an isolated PRO1100polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 to about 320, inclusive of FIG. 216 (SEQ ID NO:299).

[1787] In a further aspect, the invention concerns an isolated PRO1100polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 320 of FIG. 216 (SEQ ID NO:299).

[1788] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1100 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 320,inclusive of FIG. 216 (SEQ ID NO:299), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1789] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1100 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1100 antibody.

[1790] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1100 polypeptide, bycontacting the native PRO1100 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1791] In a still further embodiment, the invention concerns acomposition comprising a PRO1100 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1792] 94. PRO836

[1793] A cDNA clone (DNA59620-1463) has been identified, having somesequence identity with SLS1 that encodes a novel polypeptide, designatedin the present application as “PRO836.”

[1794] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO836 polypeptide.

[1795] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO836 polypeptide having the sequence of amino acidresidues from about 1 or 30 to about 461, inclusive of FIG. 218 (SEQ IDNO:301), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-461, or in anotherembodiment, 30-461.

[1796] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO836 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 65 or 152and about 1447, inclusive, of FIG. 217 (SEQ ID NO:300). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1797] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209989 (DNA59620-1463), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209989 (DNA59620-1463).

[1798] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 30 to about 461, inclusive of FIG.218 (SEQ ID NO:301), or the complement of the DNA of (a).

[1799] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO836polypeptide having the sequence of amino acid residues from about 1 or30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1800] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301), or (b) thecomplement of the DNA of (a).

[1801] In another embodiment, the invention provides isolated PRO836polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1802] In a specific aspect, the invention provides isolated nativesequence PRO836 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 30 through 461 of FIG. 218 (SEQID NO:301).

[1803] In another aspect, the invention concerns an isolated PRO836polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 30 to about 461, inclusive of FIG. 218 (SEQ ID NO:301).

[1804] In a further aspect, the invention concerns an isolated PRO836polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 30through 461 of FIG. 218 (SEQ ID NO:301).

[1805] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO836 polypeptide havingthe sequence of amino acid residues from about 1 or 30 to about 461,inclusive of FIG. 218 (SEQ ID NO:301), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1806] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO836 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO836 antibody.

[1807] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO836 polypeptide, bycontacting the native PRO836 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1808] In a still further embodiment, the invention concerns acomposition comprising a PRO836 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1809] 95. PRO1141

[1810] A cDNA clone (DNA59625-1498) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO1141”.

[1811] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1141 polypeptide.

[1812] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1141 polypeptide having the sequence of aminoacid residues from about 1 or about 20 to about 247, inclusive of FIG.220 (SEQ ID NO:303), or (b) the complement of the DNA molecule of (a).

[1813] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1141 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 204 orabout 261 and about 944, inclusive, of FIG. 219 (SEQ ID NO:302).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1814] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209992 (DNA59625-1498) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209992 (DNA59625-1498).

[1815] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 20 to about 247, inclusive of FIG. 220(SEQ ID NO:303), or (b) the complement of the DNA of (a).

[1816] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1141 polypeptide having the sequence of amino acidresidues from 1 or about 20 to about 247, inclusive of FIG. 220 (SEQ IDNO:303), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1817] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1141 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 19 in thesequence of FIG. 220 (SEQ ID NO:303). The transmembrane domains havebeen tentatively identified as extending from about amino acid position38 to about amino acid position 57, from about amino acid position 67 toabout amino acid position 83, from about amino acid position 117 toabout amino acid position 139 and from about amino acid position 153 toabout amino acid position 170, in the PRO1141 amino acid sequence (FIG.220, SEQ ID NO:303).

[1818] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303), or (b)the complement of the DNA of (a).

[1819] Another embodiment is directed to fragments of a PRO1141polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 219 (SEQ ID NO:302).

[1820] In another embodiment, the invention provides isolated PRO1141polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1821] In a specific aspect, the invention provides isolated nativesequence PRO1141 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 20 to about 247 ofFIG. 220 (SEQ ID NO:303).

[1822] In another aspect, the invention concerns an isolated PRO1141polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303).

[1823] In a further aspect, the invention concerns an isolated PRO1141polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303).

[1824] In yet another aspect, the invention concerns an isolated PRO1141polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 247, inclusive of FIG. 220 (SEQ ID NO:303), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1141antibody. Preferably, the PRO1141 fragment retains a qualitativebiological activity of a native PRO1141 polypeptide.

[1825] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1141 polypeptide havingthe sequence of amino acid residues from about 1 or about 20 to about247, inclusive of FIG. 220 (SEQ ID NO:303), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1826] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA33128 comprising thenucleotide sequence of SEQ ID NO:304 (see FIG. 221).

[1827] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA34256 comprising thenucleotide sequence of SEQ ID NO:305 (see FIG. 222).

[1828] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA47941 comprising thenucleotide sequence of SEQ ID NO:306 (see FIG. 223).

[1829] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA54389 comprising thenucleotide sequence of SEQ ID NO:307 (see FIG. 224).

[1830] 96. PRO1132

[1831] A cDNA clone (DNA59767-1489) has been identified that encodes anovel polypeptide having sequence identity with serine proteases andtrypsinogen and designated in the present application as “PRO1132.”

[1832] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1132 polypeptide.

[1833] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1132 polypeptide having the sequence of aminoacid residues from about 23 to about 293, inclusive of FIG. 226 (SEQ IDNO:309), or (b) the complement of the DNA molecule of (a).

[1834] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1132 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 420 andabout 1232, inclusive, of FIG. 225 (SEQ ID NO:308). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1835] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203108 (DNA59767-1489), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203108 (DNA59767-1489).

[1836] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 23 to about 293, inclusive of FIG. 226(SEQ ID NO:309), or the complement of the DNA of (a).

[1837] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1132 polypeptide having the sequence of amino acid residues fromabout 23 to about 293, inclusive of FIG. 226 (SEQ ID NO:309), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1838] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 293, inclusive of FIG. 226 (SEQ ID NO:309), or (b) thecomplement of the DNA of (a).

[1839] Another embodiment is directed to fragments of a PRO1132polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1840] In another embodiment, the invention provides isolated PRO1132polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1841] In a specific aspect, the invention provides isolated nativesequence PRO1132 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 23 through 293 of FIG. 226 (SEQ IDNO:309).

[1842] In another aspect, the invention concerns an isolated PRO1132polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 293, inclusive of FIG. 226 (SEQ ID NO:309).

[1843] In a further aspect, the invention concerns an isolated PRO1132polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23through 293 of FIG. 226 (SEQ ID NO:309).

[1844] In yet another aspect, the invention concerns an isolated PRO1132polypeptide, comprising the sequence of amino acid residues 23 to about293, inclusive of FIG. 226 (SEQ ID NO:309), or a fragment thereofsufficient to provide a binding site for an anti-PRO1132 antibody.Preferably, the PRO1132 fragment retains a qualitative biologicalactivity of a native PRO1132 polypeptide.

[1845] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1132 polypeptide havingthe sequence of amino acid residues from about 23 to about 293,inclusive of FIG. 226 (SEQ ID NO:309), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1846] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1132 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1132 antibody.

[1847] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1132 polypeptide, bycontacting the native PRO1132 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1848] In a still further embodiment, the invention concerns acomposition comprising a PRO1132 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1849] 97. PRO1346

[1850] A cDNA clone (DNA59776-1600) has been identified, that encodes anovel polypeptide, designated in the present application as PRO1346 (orNL7), having homology to known TIE ligands.

[1851] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding an NL7 polypeptide.

[1852] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding an NL7 polypeptide having the sequence of amino acidresidues from about 51 to about 461, inclusive of FIG. 228 (SEQ IDNO:314), or (b) the complement of the DNA molecule of (a).

[1853] In another aspect, the invention concerns an isolated nucleicacid molecule encoding an NL7 polypeptide comprising DNA hybridizing tothe complement of the nucleic acid between about nucleotides 1-3 (ATG)and about 1381-1383 (CGC, preceding the TAG stop codon), inclusive, ofFIG. 227 (SEQ ID NO:313). Preferably, hybridization occurs understringent hybridization and wash conditions.

[1854] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203128 (DNA59776-1600), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203128 (DNA59776-1600).

[1855] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 51 to about 461, inclusive of FIG. 228(SEQ ID NO:314), or the complement of the DNA of (a).

[1856] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 1000 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding an NL7 polypeptide having the sequence of aminoacid residues from about 51 to about 461, inclusive of FIG. 228 (SEQ IDNO:314), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1857] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding an NL7 polypeptide, with orwithout the initiating methionine, or its soluble forms, i.e.transmembrane domain deleted or inactivated variants, or iscomplementary to such encoding nucleic acid molecule. The transmembranedomain has been tentatively identified as extending from about aminoacid position 31 to about amino acid position 50 in the NL7 amino acidsequence (FIG. 228, SEQ ID NO:314).

[1858] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 51to about 461, inclusive of FIG. 228 (SEQ ID NO:314), or (b) thecomplement of the DNA of (a).

[1859] In a further aspect, the invention concerns an isolated nucleicacid molecule, at least about 200 bases in length, which encodes afragment of a native NL7 polypeptide.

[1860] In another embodiment, the invention provides an isolated NL7polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1861] In a specific aspect, the invention provides an isolated nativesequence NL7 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues from about 51 to about 461 of FIG. 228(SEQ ID NO:314).

[1862] In another aspect, the invention concerns an isolated NL7polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residuesfrom about 51 to about 461, inclusive of FIG. 228 (SEQ ID NO:314).

[1863] In a further aspect, the invention concerns an isolated NL7polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 51 to461 of FIG. 228 (SEQ ID NO:314).

[1864] In yet another aspect, the invention concerns an isolated NL7polypeptide, comprising the sequence of amino acid residues from about51 to about 461, inclusive of FIG. 228 (SEQ ID NO:314), or a fragmentthereof sufficient to provide a binding site for an anti-NL7 antibody.Preferably, the NL7 fragment retains a qualitative biological activityof a native NL7 polypeptide.

[1865] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding an NL7 polypeptide havingthe sequence of amino acid residues from about 51 to about 461,inclusive of FIG. 228 (SEQ ID NO:314), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1866] In yet another embodiment, the invention concerns agonists andantagonists of the a native NL7 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-NL7 antibody.

[1867] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native NL7 polypeptide, bycontacting the native NL7 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1868] In a still further embodiment, the invention concerns acomposition comprising an NL7 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1869] 98. PRO1131

[1870] A cDNA clone (DNA59777-1480) has been identified that encodes anovel polypeptide having sequence identity with LDL receptors anddesignated in the present application as “PRO1131.”

[1871] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1131 polypeptide.

[1872] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1131 polypeptide having the sequence of aminoacid residues from about 1 to about 280, inclusive of FIG. 230 (SEQ IDNO:319), or (b) the complement of the DNA molecule of (a).

[1873] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1131 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 144 andabout 983, inclusive, of FIG. 229 (SEQ ID NO:318). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1874] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203111 (DNA59777-1480), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203111 (DNA59777-1480).

[1875] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 280, inclusive of FIG. 230(SEQ ID NO:319), or the complement of the DNA of (a).

[1876] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1131 polypeptide having the sequence of amino acid residues fromabout 1 to about 280, inclusive of FIG. 230 (SEQ ID NO:319), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1877] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1131 polypeptide in itssoluble form, i.e. transmembrane domain deleted or inactivated variants,or is complementary to such encoding nucleic acid molecule. Thetransmembrane domain (type II) has been tentatively identified asextending from about amino acid positions 49-74 in the amino acidsequence of FIG. 230, SEQ ID NO:319.

[1878] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 280, inclusive of FIG. 230 (SEQ ID NO:319), or (b) thecomplement of the DNA of (a).

[1879] Another embodiment is directed to fragments of a PRO1131polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1880] In another embodiment, the invention provides isolated PRO1131polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1881] In a specific aspect, the invention provides isolated nativesequence PRO1131 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 280 of FIG. 230 (SEQ IDNO:319).

[1882] In another aspect, the invention concerns an isolated PRO1131polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 280, inclusive of FIG. 230 (SEQ ID NO:319).

[1883] In a further aspect, the invention concerns an isolated PRO1131polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 280 of FIG. 230 (SEQ ID NO:319).

[1884] In yet another aspect, the invention concerns an isolated PRO1131polypeptide, comprising the sequence of amino acid residues 1 to about280, inclusive of FIG. 230 (SEQ ID NO:319), or a fragment thereofsufficient to provide a binding site for an anti-PRO1131 antibody.Preferably, the PRO1131 fragment retains a qualitative biologicalactivity of a native PRO1131 polypeptide.

[1885] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1131 polypeptide havingthe sequence of amino acid residues from about 1 to about 280, inclusiveof FIG. 230 (SEQ ID NO:319), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1886] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1131 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1131 antibody.

[1887] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1131 polypeptide, bycontacting the native PRO1131 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1888] In a still further embodiment, the invention concerns acomposition comprising a PRO1131 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1889] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA43546 comprising thenucleotide sequence of FIG. 231 (SEQ ID NO:320).

[1890] 99. PRO1281

[1891] A cDNA clone (DNA59820-1549) has been identified that encodes anovel secreted polypeptide designated in the present application as“PRO1281”.

[1892] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1281 polypeptide.

[1893] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1281 polypeptide having the sequence of aminoacid residues from about 16 to about 775, inclusive of FIG. 233 (SEQ IDNO:326), or (b) the complement of the DNA molecule of (a).

[1894] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1281 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 273 andabout 2552, inclusive, of FIG. 232 (SEQ ID NO:325). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1895] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203129 (DNA59820-1549), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203129 (DNA59820-1549).

[1896] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 16 to about 775, inclusive of FIG. 233(SEQ ID NO:326), or the complement of the DNA of (a).

[1897] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1281 polypeptide having the sequence of amino acid residues fromabout 16 to about 775, inclusive of FIG. 233 (SEQ ID NO:326), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1898] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1281 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 15 in the sequence of FIG.233 (SEQ ID NO:326).

[1899] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 16to about 775, inclusive of FIG. 233 (SEQ ID NO:326), or (b) thecomplement of the DNA of (a).

[1900] Another embodiment is directed to fragments of a PRO1281polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1901] In another embodiment, the invention provides isolated PRO1281polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1902] In a specific aspect, the invention provides isolated nativesequence PRO1281 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 16 to 775 of FIG. 233 (SEQ ID NO:326).

[1903] In another aspect, the invention concerns an isolated PRO1281polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues16 to about 775, inclusive of FIG. 233 (SEQ ID NO:326).

[1904] In a further aspect, the invention concerns an isolated PRO1281polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 16 to775 of FIG. 233 (SEQ ID NO:326).

[1905] In yet another aspect, the invention concerns an isolated PRO1281polypeptide, comprising the sequence of amino acid residues 16 to about775, inclusive of FIG. 233 (SEQ ID NO:326), or a fragment thereofsufficient to provide a binding site for an anti-PRO1281 antibody.Preferably, the PRO1281 fragment retains a qualitative biologicalactivity of a native PRO1281 polypeptide.

[1906] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1281 polypeptide havingthe sequence of amino acid residues from about 16 to about 775,inclusive of FIG. 233 (SEQ ID NO:326), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1907] 100. PRO1064

[1908] A cDNA clone (DNA59827-1426) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO1064”.

[1909] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1064 polypeptide.

[1910] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1064 polypeptide having the sequence of aminoacid residues from about 1 or about 25 to about 153, inclusive of FIG.235 (SEQ ID NO:334), or (b) the complement of the DNA molecule of (a).

[1911] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1064 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 532 orabout 604 and about 990, inclusive, of FIG. 234 (SEQ ID NO:333).Preferably, hybridization occurs under stringent hybridization and washconditions.

[1912] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203089 (DNA59827-1426) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203089 (DNA59827-1426).

[1913] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 25 to about 153, inclusive of FIG. 235(SEQ ID NO:334), or (b) the complement of the DNA of (a).

[1914] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1064 polypeptide having the sequence of amino acidresidues from 1 or about 25 to about 153, inclusive of FIG. 235 (SEQ IDNO:334), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[1915] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1064 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 24 in thesequence of FIG. 235 (SEQ ID NO:334). The transmembrane domain has beententatively identified as extending from about amino acid position 89 toabout amino acid position 110 in the PRO1064 amino acid sequence (FIG.235, SEQ ID NO:334).

[1916] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334), or (b)the complement of the DNA of (a).

[1917] Another embodiment is directed to fragments of a PRO1064polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 234 (SEQ ID NO:333).

[1918] In another embodiment, the invention provides isolated PRO1064polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[1919] In a specific aspect, the invention provides isolated nativesequence PRO1064 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 25 to about 153 ofFIG. 235 (SEQ ID NO:334).

[1920] In another aspect, the invention concerns an isolated PRO1064polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334).

[1921] In a further aspect, the invention concerns an isolated PRO1064polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334).

[1922] In yet another aspect, the invention concerns an isolated PRO1064polypeptide, comprising the sequence of amino acid residues 1 or about25 to about 153, inclusive of FIG. 235 (SEQ ID NO:334), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1064antibody. Preferably, the PRO1064 fragment retains a qualitativebiological activity of a native PRO1064 polypeptide.

[1923] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1064 polypeptide havingthe sequence of amino acid residues from about 1 or about 25 to about153, inclusive of FIG. 235 (SEQ ID NO:334), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[1924] In another embodiment, the invention provides an expressedsequence tag (EST) designated herein as DNA45288 comprising thenucleotide sequence of SEQ ID NO:335 (see FIG. 236).

[1925] 101. PRO1379

[1926] A cDNA clone (DNA59828-1608) has been identified that encodes anovel secreted polypeptide designated in the present application as“PRO1379.”

[1927] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1379 polypeptide.

[1928] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1379 polypeptide having the sequence of aminoacid residues from about 18 to about 574, inclusive of FIG. 238 (SEQ IDNO:340), or (b) the complement of the DNA molecule of (a).

[1929] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1379 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 61 andabout 1731, inclusive, of FIG. 237 (SEQ ID NO:339). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1930] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203158 (DNA59828-1608), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203158 (DNA59828-1608).

[1931] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 18 to about 574, inclusive of FIG. 238(SEQ ID NO:340), or the complement of the DNA of (a).

[1932] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1379 polypeptide having the sequence of amino acid residues fromabout 18 to about 574, inclusive of FIG. 238 (SEQ ID NO:340), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1933] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1379 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 17 in the sequence of FIG.238 (SEQ ID NO:340).

[1934] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 574, inclusive of FIG. 238 (SEQ ID NO:340), or (b) thecomplement of the DNA of (a).

[1935] Another embodiment is directed to fragments of a PRO1379polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[1936] In another embodiment, the invention provides isolated PRO1379polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1937] In a specific aspect, the invention provides isolated nativesequence PRO1379 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 18 to 574 of FIG. 238 (SEQ ID NO:340).

[1938] In another aspect, the invention concerns an isolated PRO1379polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 574, inclusive of FIG. 238 (SEQ ID NO:340).

[1939] In a further aspect, the invention concerns an isolated PRO1379polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18 to574 of FIG. 238 (SEQ ID NO:340).

[1940] In yet another aspect, the invention concerns an isolated PRO1379polypeptide, comprising the sequence of amino acid residues 18 to about574, inclusive of FIG. 238 (SEQ ID NO:340), or a fragment thereofsufficient to provide a binding site for an anti-PRO1379 antibody.Preferably, the PRO1379 fragment retains a qualitative biologicalactivity of a native PRO1379 polypeptide.

[1941] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1379 polypeptide havingthe sequence of amino acid residues from about 18 to about 574,inclusive of FIG. 238 (SEQ ID NO:340), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1942] 102. PRO844

[1943] A cDNA clone (DNA59838-1462) has been identified, having sequenceidentity with protease inhibitors, that encodes a novel polypeptide,designated in the present application as “PRO844.”

[1944] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO844 polypeptide.

[1945] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO844 polypeptide having the sequence of amino acidresidues from about 1 or 20 to about 111, inclusive of FIG. 240 (SEQ IDNO:345), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-111, or in anotherembodiment, 20-111.

[1946] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO844 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 5 or 62 andabout 337, inclusive, of FIG. 239 (SEQ ID NO:344). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1947] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209976 (DNA59838-1462), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209976 (DNA59838-1462).

[1948] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 20 to about 111, inclusive of FIG.240 (SEQ ID NO:345), or the complement of the DNA of (a).

[1949] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO844polypeptide having the sequence of amino acid residues from about 1 or20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1950] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345), or (b) thecomplement of the DNA of (a).

[1951] In another embodiment, the invention provides isolated PRO844polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1952] In a specific aspect, the invention provides isolated nativesequence PRO844 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 20 through 111 of FIG. 240 (SEQID NO:345).

[1953] In another aspect, the invention concerns an isolated PRO844polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 20 to about 111, inclusive of FIG. 240 (SEQ ID NO:345).

[1954] In a further aspect, the invention concerns an isolated PRO844polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 20through 111 of FIG. 240 (SEQ ID NO:345).

[1955] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO844 polypeptide havingthe sequence of amino acid residues from about 1 or 20 to about 111,inclusive of FIG. 240 (SEQ ID NO:345), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1956] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO844 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO844 antibody.

[1957] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO844 polypeptide, bycontacting the native PRO844 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1958] In a still further embodiment, the invention concerns acomposition comprising a PRO844 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1959] 103. PRO848

[1960] A cDNA clone (DNA59839-1461) has been identified, having sequenceidentity with sialytransferases that encodes a novel polypeptide,designated in the present application as “PRO848.”

[1961] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO848 polypeptide.

[1962] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO848 polypeptide having the sequence of amino acidresidues from about 1 or 36 to about 600, inclusive of FIG. 242 (SEQ IDNO:347), or (b) the complement of the DNA molecule of (a). The term “or”as used herein to refer to amino or nucleic acids is meant to refer totwo alternative embodiments provided herein, i.e., 1-600, or in anotherembodiment, 36-600.

[1963] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO848 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 1 or 251and about 1945, inclusive, of FIG. 241 (SEQ ID NO:346). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1964] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209988 (DNA59839-1461), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209988 (DNA59839-1461).

[1965] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 36 to about 600, inclusive of FIG.242 (SEQ ID NO:347), or the complement of the DNA of (a).

[1966] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO848polypeptide having the sequence of amino acid residues from about 1 or36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1967] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347), or (b) thecomplement of the DNA of (a).

[1968] In another embodiment, the invention provides isolated PRO848polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1969] In a specific aspect, the invention provides isolated nativesequence PRO848 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 36 through 600 of FIG. 242 (SEQID NO:347).

[1970] In another aspect, the invention concerns an isolated PRO848polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 36 to about 600, inclusive of FIG. 242 (SEQ ID NO:347).

[1971] In a further aspect, the invention concerns an isolated PRO848polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 36through 600 of FIG. 242 (SEQ ID NO:347).

[1972] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO848 polypeptide havingthe sequence of amino acid residues from about 1 or 36 to about 600,inclusive of FIG. 242 (SEQ ID NO:347), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1973] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO848 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO848 antibody.

[1974] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO848 polypeptide, bycontacting the native PRO848 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1975] In a still further embodiment, the invention concerns acomposition comprising a PRO848 polypeptide, or an agonist or antagonistas hereinabove defined, in combination with a pharmaceuticallyacceptable carrier.

[1976] 104. PRO1097

[1977] Applicants have identified a cDNA clone (DNA59841-1460) thatencodes a novel secreted polypeptide having domains therein from theglycoprotease family proteins and the acyltransferase ChoActase/COT/CPTfamily, wherein the polypeptide is designated in the present applicationas “PRO1097”.

[1978] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1097 polypeptide.

[1979] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1097 polypeptide having the sequence of aminoacid residues from about 1 or 21 to about 91, inclusive of FIG. 244 (SEQID NO:349), or (b) the complement of the DNA molecule of (a). The term“or” as used herein to refer to amino or nucleic acids is meant to referto two alternative embodiments provided herein, i.e., 1-91, or inanother embodiment, 21-91.

[1980] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1097 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 3 or 63 andabout 275, inclusive, of FIG. 243 (SEQ ID NO:348). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1981] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203044 (DNA59841-1460), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203044 (DNA59841-1460).

[1982] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 21 to about 91, inclusive of FIG.244 (SEQ ID NO:349), or the complement of the DNA of (a).

[1983] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1097polypeptide having the sequence of amino acid residues from about 1 or21 to about 91, inclusive of FIG. 244 (SEQ ID NO:349), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[1984] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1097 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 20 in thesequence of FIG. 244 (SEQ ID NO:349).

[1985] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 21 to about 91, inclusive of FIG. 244 (SEQ ID NO:349), or (b) thecomplement of the DNA of (a).

[1986] In another embodiment, the invention provides isolated PRO1097polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[1987] In a specific aspect, the invention provides isolated nativesequence PRO1097 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 21 through 91 of FIG. 244 (SEQ IDNO:349).

[1988] In another aspect, the invention concerns an isolated PRO1097polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 21 to about 91, inclusive of FIG. 244 (SEQ ID NO:349).

[1989] In a further aspect, the invention concerns an isolated PRO1097polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 21through 91 of FIG. 244 (SEQ ID NO:349).

[1990] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1097 polypeptide havingthe sequence of amino acid residues from about 1 or 21 to about 91,inclusive of FIG. 244 (SEQ ID NO:349), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[1991] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1097 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1097 antibody.

[1992] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1097 polypeptide, bycontacting the native PRO1097 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[1993] In a still further embodiment, the invention concerns acomposition comprising a PRO1097 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[1994] 105. PRO1153

[1995] A cDNA clone (DNA59842-1502) has been identified, having twotransmembrane domains and being very proline rich, that encodes a novelpolypeptide, designated in the present application as “PRO1153.”

[1996] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1153 polypeptide.

[1997] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1153 polypeptide having the sequence of aminoacid residues from about 1 to about 197, inclusive of FIG. 246 (SEQ IDNO:351), or (b) the complement of the DNA molecule of (a).

[1998] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1153 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 92 andabout 682, inclusive, of FIG. 245 (SEQ ID NO:350). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[1999] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209982 (DNA59842-1502), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209982 (DNA59842-1502).

[2000] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 197, inclusive of FIG. 246(SEQ ID NO:351), or the complement of the DNA of (a).

[2001] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1153polypeptide having the sequence of amino acid residues from about 1 toabout 197, inclusive of FIG. 246 (SEQ ID NO:351), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[2002] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1153 polypeptide, and itssoluble, i.e. transmembrane domain deleted or inactivated variants, oris complementary to such encoding nucleic acid molecule. Thetransmembrane domains have been tentatively identified as extending fromabout amino acid positions 10-28 and 85-110 in the PRO1153 amino acidsequence (FIG. 246, SEQ ID NO:351).

[2003] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 197, inclusive of FIG. 246 (SEQ ID NO:351), or (b) thecomplement of the DNA of (a).

[2004] In another embodiment, the invention provides isolated PRO1153polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2005] In a specific aspect, the invention provides isolated nativesequence PRO1153 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 197 of FIG. 246 (SEQ ID NO:351).

[2006] In another aspect, the invention concerns an isolated PRO1153polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 197, inclusive of FIG. 246 (SEQ ID NO:351).

[2007] In a further aspect, the invention concerns an isolated PRO1153polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 197 of FIG. 246 (SEQ ID NO:351).

[2008] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1153 polypeptide havingthe sequence of amino acid residues from about 1 to about 197, inclusiveof FIG. 246 (SEQ ID NO:351), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2009] 106. PRO1154

[2010] A cDNA clone (DNA59846-1503) has been identified that encodes anovel aminopeptidase, designated in the present application as“PRO1154.”

[2011] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1154 polypeptide.

[2012] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1154 polypeptide having the sequence of aminoacid residues from about 1 or 35 to about 941, inclusive of FIG. 248(SEQ ID NO:353), or (b) the complement of the DNA molecule of (a).

[2013] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1154 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 86 or 188and about 2908, inclusive, of FIG. 247 (SEQ ID NO:352). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2014] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209978 (DNA59846-1503), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209978 (DNA59846-1503).

[2015] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 35 to about 941, inclusive of FIG.248 (SEQ ID NO:353), or the complement of the DNA of (a).

[2016] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1154polypeptide having the sequence of amino acid residues from about 1 or35 to about 941, inclusive of FIG. 258 (SEQ ID NO:353), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2017] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 35 to about 941, inclusive of FIG. 248 (SEQ ID NO:353), or (b) thecomplement of the DNA of (a).

[2018] In another aspect, the invention concerns an isolated nucleicacid molecule consisting essentially of DNA encoding a polypeptidehaving amino acids 1 or 35 through about 73 of SEQ ID NO:353.

[2019] In another embodiment, the invention provides isolated PRO1154polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2020] In a specific aspect, the invention provides isolated nativesequence PRO1154 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 35 to 941 of FIG. 248 (SEQ IDNO:353).

[2021] In a specific aspect, the invention provides a polypeptide havingamino acids 1 or 35 through about 73 of SEQ ID NO:353.

[2022] In another aspect, the invention concerns an isolated PRO1154polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 35 to about 941, inclusive of FIG. 248 (SEQ ID NO:353).

[2023] In a further aspect, the invention concerns an isolated PRO1154polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 35through 941 of FIG. 248 (SEQ ID NO:353).

[2024] In yet another aspect, the invention concerns an isolated PRO1154polypeptide, comprising the sequence of amino acid residues 1 or 35 toabout 941, inclusive of FIG. 248 (SEQ ID NO:353), or a fragment thereofsufficient to provide a binding site for an anti-PRO1154 antibody.Preferably, the PRO1154 fragment retains a qualitative biologicalactivity of a native PRO1154 polypeptide.

[2025] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1154 polypeptide havingthe sequence of amino acid residues from about 1 or 35 to about 941,inclusive of FIG. 248 (SEQ ID NO:353), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2026] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1154 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1154 antibody.

[2027] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1154 polypeptide, bycontacting the native PRO1154 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2028] In a still further embodiment, the invention concerns acomposition comprising a PRO1154 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2029] 107. PRO1181

[2030] A cDNA clone (DNA59847-1511) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1181.”

[2031] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1181 polypeptide.

[2032] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1181 polypeptide having the sequence of aminoacid residues from about 1 or about 16 to about 437, inclusive of FIG.250 (SEQ ID NO:355), or (b) the complement of the DNA molecule of (a).

[2033] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1181 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 17 orabout 62 and about 1327, inclusive, of FIG. 249 (SEQ ID NO:354).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2034] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203098 (DNA59847-1511) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203098 (DNA59847-1511).

[2035] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 16 to about 437, inclusive of FIG. 250(SEQ ID NO:355), or (b) the complement of the DNA of (a).

[2036] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1181 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 437, inclusive of FIG. 250 (SEQ IDNO:355), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2037] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1181 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionineor is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 15 in the sequence of FIG.250 (SEQ ID NO:355). The transmembrane domain is at amino acidspositions 243-260 of FIG. 250.

[2038] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355), or (b)the complement of the DNA of (a).

[2039] Another embodiment is directed to fragments of a PRO1181polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 249 (SEQ ID NO:354).

[2040] In another embodiment, the invention provides isolated PRO1181polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2041] In a specific aspect, the invention provides isolated nativesequence PRO1181 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 16 to about 437 ofFIG. 250 (SEQ ID NO:355).

[2042] In another aspect, the invention concerns an isolated PRO1181polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355).

[2043] In a further aspect, the invention concerns an isolated PRO1181polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355).

[2044] In yet another aspect, the invention concerns an isolated PRO1181polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 437, inclusive of FIG. 250 (SEQ ID NO:355), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1181antibody. Preferably, the PRO1181 fragment retains a qualitativebiological activity of a native PRO1181 polypeptide.

[2045] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1181 polypeptide havingthe sequence of amino acid residues from about 1 or about 16 to about437, inclusive of FIG. 250 (SEQ ID NO:355), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2046] 108. PRO1182

[2047] A cDNA clone (DNA59848-1512) has been identified, having homologyto nucleic acid encoding conglutinin that encodes a novel polypeptide,designated in the present application as “PRO1182”.

[2048] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1182 polypeptide.

[2049] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1182 polypeptide having the sequence of aminoacid residues from about 1 or about 26 to about 271, inclusive of FIG.252 (SEQ ID NO:357), or (b) the complement of the DNA molecule of (a).

[2050] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1182 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 67 orabout 142 and about 879, inclusive, of FIG. 251 (SEQ ID NO:356).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2051] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203088 (DNA59848-1512) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203088 (DNA59848-1512).

[2052] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 26 to about 271, inclusive of FIG. 252(SEQ ID NO:357), or (b) the complement of the DNA of (a).

[2053] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1182 polypeptide having the sequence of amino acidresidues from 1 or about 26 to about 271, inclusive of FIG. 252 (SEQ IDNO:357), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2054] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1182 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionineor is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 25 in the sequence of FIG.252 (SEQ ID NO:357).

[2055] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357), or (b)the complement of the DNA of (a).

[2056] Another embodiment is directed to fragments of a PRO1182polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 251 (SEQ ID NO:356).

[2057] In another embodiment, the invention provides isolated PRO1182polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2058] In a specific aspect, the invention provides isolated nativesequence PRO1182 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 26 to about 271 ofFIG. 252 (SEQ ID NO:357).

[2059] In another aspect, the invention concerns an isolated PRO1182polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357).

[2060] In a further aspect, the invention concerns an isolated PRO1182polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357).

[2061] In yet another aspect, the invention concerns an isolated PRO1182polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 271, inclusive of FIG. 252 (SEQ ID NO:357), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1182antibody. Preferably, the PRO1182 fragment retains a qualitativebiological activity of a native PRO1182 polypeptide.

[2062] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1182 polypeptide havingthe sequence of amino acid residues from about 1 or about 26 to about271, inclusive of FIG. 252 (SEQ ID NO:357), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2063] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1182 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1182 antibody.

[2064] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1182 polypeptide bycontacting the native PRO1182 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2065] In a still further embodiment, the invention concerns acomposition comprising a PRO1182 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2066] 109. PRO1155

[2067] A cDNA clone (DNA59849-1504) has been identified, having sequenceidentity with neurokinin B that encodes a novel polypeptide, designatedin the present application as “PRO1155.”

[2068] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1155 polypeptide.

[2069] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1155 polypeptide having the sequence of aminoacid residues from about 1 or 19 to about 135, inclusive of FIG. 254(SEQ ID NO:359), or (b) the complement of the DNA molecule of (a). Theterm “or” as used herein to refer to nucleic or amino acids is meant toconvey alternative embodiments, i.e., 1-135 or alternatively in anotherembodiment, 19-135.

[2070] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1155 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 158 or 212and about 562, inclusive, of FIG. 253 (SEQ ID NO:358). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2071] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209986 (DNA59849-1504), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209986 (DNA59849-1504).

[2072] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 19 to about 135, inclusive of FIG.254 (SEQ ID NO:359), or the complement of the DNA of (a).

[2073] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1155polypeptide having the sequence of amino acid residues from about 19 toabout 135, inclusive of FIG. 254 (SEQ ID NO:359), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[2074] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 19 to about 135, inclusive of FIG. 254 (SEQ ID NO:359), or (b) thecomplement of the DNA of (a).

[2075] In another embodiment, the invention provides isolated PRO1155polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2076] In a specific aspect, the invention provides isolated nativesequence PRO1155 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 19 through 135 of FIG. 254 (SEQID NO:359).

[2077] In another aspect, the invention concerns an isolated PRO1155polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 19 to about 135, inclusive of FIG. 254 (SEQ ID NO:359).

[2078] In a further aspect, the invention concerns an isolated PRO1155polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 19through 135 of FIG. 254 (SEQ ID NO:359).

[2079] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1155 polypeptide havingthe sequence of amino acid residues from about 1 or 19 to about 135,inclusive of FIG. 254 (SEQ ID NO:359), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2080] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1155 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1155 antibody.

[2081] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1155 polypeptide, bycontacting the native PRO1155 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2082] In a still further embodiment, the invention concerns acomposition comprising a PRO1155 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2083] 110. PRO1156

[2084] A cDNA clone (DNA59853-1505) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1156.”

[2085] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1156 polypeptide.

[2086] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1156 polypeptide having the sequence of aminoacid residues from about 23 to about 159, inclusive of FIG. 256 (SEQ IDNO:361), or (b) the complement of the DNA molecule of (a).

[2087] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1156 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 281 andabout 688, inclusive, of FIG. 255 (SEQ ID NO:360). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2088] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209985 (DNA59853-1505), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209985 (DNA59853-1505).

[2089] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 23 to about 159, inclusive of FIG. 256(SEQ ID NO:361), or the complement of the DNA of (a).

[2090] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 50 nucleotides, preferably at least 100nucleotides, and produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1156polypeptide having the sequence of amino acid residues from about 23 toabout 159, inclusive of FIG. 256 (SEQ ID NO:361), or (b) the complementof the DNA molecule of (a), and, if the DNA molecule has at least aboutan 80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b),isolating the test DNA molecule.

[2091] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1156 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 to about amino acid position 22 in the sequence of FIG. 256(SEQ ID NO:361).

[2092] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 159, inclusive of FIG. 256 (SEQ ID NO:361), or (b) thecomplement of the DNA of (a).

[2093] In another aspect, the invention concerns hybridization probesthat comprise fragments of the PRO784 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 20 to about 50 nucleotides.

[2094] In another embodiment, the invention provides isolated PRO1156polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2095] In a specific aspect, the invention provides isolated nativesequence PRO1156 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 23 to 159 of FIG. 256 (SEQ ID NO:361).

[2096] In another aspect, the invention concerns an isolated PRO1156polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 159, inclusive of FIG. 256 (SEQ ID NO:361).

[2097] In a further aspect, the invention concerns an isolated PRO1156polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23 to159 of FIG. 256 (SEQ ID NO:361).

[2098] In yet another aspect, the invention concerns an isolated PRO1156polypeptide, comprising the sequence of amino acid residues 23 to about159, inclusive of FIG. 256 (SEQ ID NO:361), or a fragment thereofsufficient to provide a binding site for an anti-PRO1156 antibody.Preferably, the PRO1156 fragment retains a qualitative biologicalactivity of a native PRO1156 polypeptide.

[2099] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1156 polypeptide havingthe sequence of amino acid residues from about 23 to about 159,inclusive of FIG. 256 (SEQ ID NO:361), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2100] 111. PRO1098

[2101] A cDNA clone (DNA59854-1459) has been identified which encodes anovel polypeptide, designated in the present application as “PRO1098.”

[2102] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1098 polypeptide.

[2103] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1098 polypeptide having the sequence of aminoacid residues from about 1 or 20 to about 78, inclusive of FIG. 258 (SEQID NO:363), or (b) the complement of the DNA molecule of (a). The term“or” as used herein to refer to amino or nucleic acids is meant to referto two alternative embodiments provided herein, i.e., 1-78, or inanother embodiment, 20-78.

[2104] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1098 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 58 or 115and about 291, inclusive, of FIG. 257 (SEQ ID NO:362). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2105] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209974 (DNA59854-1459), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209974 (DNA59854-1459).

[2106] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 20 to about 78, inclusive of FIG.258 (SEQ ID NO:363), or the complement of the DNA of (a).

[2107] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1098polypeptide having the sequence of amino acid residues from about 1 or20 to about 78, inclusive of FIG. 258 (SEQ ID NO:363), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2108] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 20 to about 78, inclusive of FIG. 258 (SEQ ID NO:363), or (b) thecomplement of the DNA of (a).

[2109] In another embodiment, the invention provides isolated PRO1098polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2110] In a specific aspect, the invention provides isolated nativesequence PRO1098 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 20 through 78 of FIG. 258 (SEQ IDNO:363).

[2111] In another aspect, the invention concerns an isolated PRO1098polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 20 to about 78, inclusive of FIG. 258 (SEQ ID NO:363).

[2112] In a further aspect, the invention concerns an isolated PRO1098polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 20through 78 of FIG. 258 (SEQ ID NO:363).

[2113] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1098 polypeptide havingthe sequence of amino acid residues from about 1 or 20 to about 78,inclusive of FIG. 258 (SEQ ID NO:363), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2114] 112. PRO1127

[2115] A cDNA clone (DNA60283-1484) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO127.”

[2116] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1127 polypeptide.

[2117] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1127 polypeptide having the sequence of aminoacid residues from about 1 or 30 to about 67, inclusive of FIG. 260 (SEQID NO:365), or (b) the complement of the DNA molecule of (a). The term“or” in reference to amino or nucleic acids as used herein refers to twoalternative embodiments, i.e., 1-67 in one embodiment, or alternatively,30-67.

[2118] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1127 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 126 or 213and about 326, inclusive, of FIG. 259 (SEQ ID NO:364). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2119] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203043 (DNA60283-1484), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203043 (DNA60283-1484).

[2120] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 30 to about 67, inclusive of FIG.260 (SEQ ID NO:365), or the complement of the DNA of (a).

[2121] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1127polypeptide having the sequence of amino acid residues from about 1 or30 to about 67, inclusive of FIG. 260 (SEQ ID NO:365), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2122] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1127 polypeptide without theN-terminal signal sequence and/or the initiating methionine. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 29 in the sequence of FIG.260 (SEQ ID NO:365).

[2123] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 30 to about 67, inclusive of FIG. 260 (SEQ ID NO:365), or (b) thecomplement of the DNA of (a).

[2124] Another embodiment is directed to fragments of a PRO1127polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[2125] In another embodiment, the invention provides isolated PRO1127polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2126] In a specific aspect, the invention provides isolated nativesequence PRO1127 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 30 through 67 of FIG. 260 (SEQ IDNO:365).

[2127] In another aspect, the invention concerns an isolated PRO1127polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 30 to about 67, inclusive of FIG. 260 (SEQ ID NO:365).

[2128] In a further aspect, the invention concerns an isolated PRO1127polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 30through 67 of FIG. 260 (SEQ ID NO:365).

[2129] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1127 polypeptide havingthe sequence of amino acid residues from about 1 or 30 to about 67,inclusive of FIG. 260 (SEQ ID NO:365), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2130] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1127 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1127 antibody.

[2131] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1127 polypeptide, bycontacting the native PRO1127 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2132] In a still further embodiment, the invention concerns acomposition comprising a PRO1127 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2133] 113. PRO1126

[2134] A cDNA clone (DNA60615-1483) has been identified, having homologyto nucleic acid encoding olfactomedin that encodes a novel polypeptide,designated in the present application as “PRO1126”.

[2135] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1126 polypeptide.

[2136] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1126 polypeptide having the sequence of aminoacid residues from about 1 or about 26 to about 402, inclusive of FIG.262 (SEQ ID NO:367), or (b) the complement of the DNA molecule of (a).

[2137] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1126 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 110 orabout 185 and about 1315, inclusive, of FIG. 261 (SEQ ID NO:366).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2138] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209980 (DNA60615-1483) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 209980 (DNA60615-1483).

[2139] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 26 to about 402, inclusive of FIG. 262(SEQ ID NO:367), or (b) the complement of the DNA of (a).

[2140] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1126 polypeptide having the sequence of amino acidresidues from 1 or about 26 to about 402, inclusive of FIG. 262 (SEQ IDNO:367), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2141] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1126 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 25 in the sequence of FIG.262 (SEQ ID NO:367).

[2142] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367), or (b)the complement of the DNA of (a).

[2143] Another embodiment is directed to fragments of a PRO1126polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 261 (SEQ ID NO:366).

[2144] In another embodiment, the invention provides isolated PRO1126polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2145] In a specific aspect, the invention provides isolated nativesequence PRO1126 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 26 to about 402 ofFIG. 262 (SEQ ID NO:367).

[2146] In another aspect, the invention concerns an isolated PRO1126polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367).

[2147] In a further aspect, the invention concerns an isolated PRO1126polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367).

[2148] In yet another aspect, the invention concerns an isolated PRO1126polypeptide, comprising the sequence of amino acid residues 1 or about26 to about 402, inclusive of FIG. 262 (SEQ ID NO:367), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1126antibody. Preferably, the PRO1126 fragment retains a qualitativebiological activity of a native PRO1126 polypeptide.

[2149] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1126 polypeptide havingthe sequence of amino acid residues from about 1 or about 26 to about402, inclusive of FIG. 262 (SEQ ID NO:367), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2150] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1126 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1126 antibody.

[2151] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1126 polypeptide bycontacting the native PRO1126 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2152] In a still further embodiment, the invention concerns acomposition comprising a PRO1126 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2153] 114. PRO1125

[2154] A cDNA clone (DNA60619-1482) has been identified, havingbeta-transducin family Trp-Asp (WD) conserved regions, that encodes anovel polypeptide, designated in the present application as “PRO1125.”

[2155] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1125 polypeptide.

[2156] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1125 polypeptide having the sequence of aminoacid residues from about 1 or 26 to about 447, inclusive of FIG. 264(SEQ ID NO:369), or (b) the complement of the DNA molecule of (a). Asused herein, “or” when referring to nucleic acids or amino acids, refersto two alternative embodiments, i.e., 1-447 and 26-447.

[2157] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1125 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 47 or 122and about 1387, inclusive, of FIG. 263 (SEQ ID NO:368). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2158] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209993 (DNA60619-1482), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209993 (DNA60619-1482).

[2159] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 26 to about 447, inclusive of FIG.264 (SEQ ID NO:369), or the complement of the DNA of (a).

[2160] In a further aspect, the invention concerns an isolated nucleicacid molecule produced by hybridizing a test DNA molecule understringent conditions with (a) a DNA molecule encoding a PRO1125polypeptide having the sequence of amino acid residues from about 1 or26 to about 447, inclusive of FIG. 264 (SEQ ID NO:369), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2161] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1125 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 25 in thesequence of FIG. 264 (SEQ ID NO:369).

[2162] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 26 to about 447, inclusive of FIG. 264 (SEQ ID NO:369), or (b) thecomplement of the DNA of (a).

[2163] In another embodiment, the invention provides isolated PRO1125polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2164] In a specific aspect, the invention provides isolated nativesequence PRO1125 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 26 to 447 of FIG. 264 (SEQ IDNO:369).

[2165] In another aspect, the invention concerns an isolated PRO1125polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 26 to about 447, inclusive of FIG. 264 (SEQ ID NO:369).

[2166] In a further aspect, the invention concerns an isolated PRO1125polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 26through 447 of FIG. 264 (SEQ ID NO:369).

[2167] In yet another aspect, the invention concerns an isolated PRO1125polypeptide, comprising the sequence of amino acid residues 26 to about447, inclusive of FIG. 264 (SEQ ID NO:369), or a fragment thereofsufficient to provide a binding site for an anti-PRO1125 antibody.Preferably, the PRO1125 fragment retains a qualitative biologicalactivity of a native PRO1125 polypeptide.

[2168] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1125 polypeptide havingthe sequence of amino acid residues from about 26 to about 447,inclusive of FIG. 264 (SEQ ID NO:369), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2169] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1125 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1125 antibody.

[2170] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1125 polypeptide, bycontacting the native PRO1125 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2171] 115. PRO1186

[2172] A cDNA clone (DNA60621-1516) has been identified that encodes anovel polypeptide having sequence identity with venom protein A anddesignated in the present application as “PRO1186.”

[2173] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1186 polypeptide.

[2174] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1186 polypeptide having the sequence of aminoacid residues from about 20 to about 105, inclusive of FIG. 266 (SEQ IDNO:371), or (b) the complement of the DNA molecule of (a).

[2175] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1186 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 148 andabout 405, inclusive, of FIG. 265 (SEQ ID NO:370). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2176] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203091 (DNA60621-1516), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203091 (DNA60621-1516).

[2177] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 20 to about 105, inclusive of FIG. 266(SEQ ID NO:371), or the complement of the DNA of (a).

[2178] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1186 polypeptide having the sequence of amino acid residues fromabout 20 to about 105, inclusive of FIG. 266 (SEQ ID NO:371), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2179] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 20to about 105, inclusive of FIG. 266 (SEQ ID NO:371), or (b) thecomplement of the DNA of (a).

[2180] Another embodiment is directed to fragments of a PRO1186polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[2181] In another embodiment, the invention provides isolated PRO1186polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2182] In a specific aspect, the invention provides isolated nativesequence PRO1186 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 20 through 105 of FIG. 266 (SEQ IDNO:371).

[2183] In another aspect, the invention concerns an isolated PRO1186polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues20 to about 105, inclusive of FIG. 266 (SEQ ID NO:371).

[2184] In a further aspect, the invention concerns an isolated PRO1186polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 20through 105 of FIG. 266 (SEQ ID NO:371).

[2185] In yet another aspect, the invention concerns an isolated PRO1186polypeptide, comprising the sequence of amino acid residues 20 to about105, inclusive of FIG. 266 (SEQ ID NO:371), or a fragment thereofsufficient to provide a binding site for an anti-PRO1186 antibody.Preferably, the PRO1186 fragment retains a qualitative biologicalactivity of a native PRO1186 polypeptide.

[2186] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1186 polypeptide havingthe sequence of amino acid residues from about 20 to about 105,inclusive of FIG. 266 (SEQ ID NO:371), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2187] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1186 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1186 antibody.

[2188] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1186 polypeptide, bycontacting the native PRO1186 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2189] In a still further embodiment, the invention concerns acomposition comprising a PRO1186 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2190] 116. PRO1198

[2191] A cDNA clone (DNA60622-1525) has been identified that encodes anovel secreted polypeptide designated in the present application as“PRO1198.”

[2192] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1198 polypeptide.

[2193] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1198 polypeptide having the sequence of aminoacid residues from about 35 to about 229, inclusive of FIG. 268 (SEQ IDNO:373), or (b) the complement of the DNA molecule of (a).

[2194] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1198 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 156 andabout 740, inclusive, of FIG. 268 (SEQ ID NO:373). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2195] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203090 (DNA60622-1525), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203090 (DNA60622-1525).

[2196] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 35 to about 229, inclusive of FIG. 268(SEQ ID NO:373), or the complement of the DNA of (a).

[2197] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1198 polypeptide having the sequence of amino acid residues fromabout 35 to about 229, inclusive of FIG. 268 (SEQ ID NO:373), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2198] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1198 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 through about amino acid position 35 in the sequence ofFIG. 268 (SEQ ID NO:373).

[2199] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 35to about 229, inclusive of FIG. 268 (SEQ ID NO:373), or (b) thecomplement of the DNA of (a).

[2200] Another embodiment is directed to fragments of a PRO1198polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2201] In another embodiment, the invention provides isolated PRO1198polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2202] In a specific aspect, the invention provides isolated nativesequence PRO1198 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 35 to 229 of FIG. 268 (SEQ ID NO:373).

[2203] In another aspect, the invention concerns an isolated PRO1198polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues35 to about 229, inclusive of FIG. 268 (SEQ ID NO:373).

[2204] In a further aspect, the invention concerns an isolated PRO1198polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 35 to229 of FIG. 268 (SEQ ID NO:373).

[2205] In yet another aspect, the invention concerns an isolated PRO1198polypeptide, comprising the sequence of amino acid residues 35 to about229, inclusive of FIG. 268 (SEQ ID NO:373), or a fragment thereofsufficient to provide a binding site for an anti-PRO1198 antibody.Preferably, the PRO1198 fragment retains a qualitative biologicalactivity of a native PRO1198 polypeptide.

[2206] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1198 polypeptide havingthe sequence of amino acid residues from about 35 to about 229,inclusive of FIG. 268 (SEQ ID NO:373), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2207] 117. PRO1158

[2208] A cDNA clone (DNA60625-1507) has been identified that encodes anovel transmembrane polypeptide, designated in the present applicationas “PRO1158”.

[2209] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1158 polypeptide.

[2210] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1158 polypeptide having the sequence of aminoacid residues from about 20 to about 123, inclusive of FIG. 270 (SEQ IDNO:375), or (b) the complement of the DNA molecule of (a).

[2211] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1158 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 220 andabout 531, inclusive, of FIG. 269 (SEQ ID NO:374). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2212] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No.209975 (DNA60625-1507), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209975 (DNA60625-1507).

[2213] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 20 to about 123, inclusive of FIG. 270(SEQ ID NO:375), or the complement of the DNA of (a).

[2214] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1158 polypeptide having the sequence of amino acid residues fromabout 20 to about 123, inclusive of FIG. 270 (SEQ ID NO:375), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2215] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1158 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 19 in thesequence of FIG. 270 (SEQ ID NO:375). The transmembrane domain has beententatively identified as extending from about amino acid position 56 toabout amino acid position 80 in the PRO1158 amino acid sequence (FIG.270, SEQ ID NO:375).

[2216] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 20to about 123, inclusive of FIG. 270 (SEQ ID NO:375), or (b) thecomplement of the DNA of (a).

[2217] In another aspect, the invention concerns hybridization probesthat comprise fragments of the PRO1158 coding sequence, or complementarysequence thereof. The hybridization probes preferably have at leastabout 20 nucleotides to about 80 nucleotides, and more preferably, atleast about 20 to about 50 nucleotides.

[2218] In another embodiment, the invention provides isolated PRO1158polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2219] In a specific aspect, the invention provides isolated nativesequence PRO1158 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 20 to 123 of FIG. 270 (SEQ ID NO:375).

[2220] In another aspect, the invention concerns an isolated PRO1158polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues20 to about 123, inclusive of FIG. 270 (SEQ ID NO:375).

[2221] In a further aspect, the invention concerns an isolated PRO1158polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 20 to123 of FIG. 270 (SEQ ID NO:375).

[2222] In yet another aspect, the invention concerns an isolated PRO1158polypeptide, comprising the sequence of amino acid residues 20 to about123, inclusive of FIG. 270 (SEQ ID NO:375), or a fragment thereofsufficient to provide a binding site for an anti-PRO1158 antibody.Preferably, the PRO1158 fragment retains a qualitative biologicalactivity of a native PRO1158 polypeptide.

[2223] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1158 polypeptide havingthe sequence of amino acid residues from about 20 to about 123,inclusive of FIG. 270 (SEQ ID NO:375), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2224] 118. PRO1159

[2225] A cDNA clone (DNA60627-1508) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1159”.

[2226] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1159 polypeptide.

[2227] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1159 polypeptide having the sequence of aminoacid residues from about 1 or about 16 to about 90, inclusive of FIG.272 (SEQ ID NO:377), or (b) the complement of the DNA molecule of (a).

[2228] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1159 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 92 orabout 137 and about 361, inclusive, of FIG. 271 (SEQ ID NO:376).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2229] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203092 (DNA60627-1508) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203092 (DNA60627-1508).

[2230] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 16 to about 90, inclusive of FIG. 272(SEQ ID NO:377), or (b) the complement of the DNA of (a).

[2231] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 10 nucleotides and produced by hybridizinga test DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1159 polypeptide having the sequence of amino acidresidues from 1 or about 16 to about 90, inclusive of FIG. 272 (SEQ IDNO:377), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, prefereably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2232] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1159 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 15 in the sequence of FIG.272 (SEQ ID NO:377).

[2233] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377), or (b)the complement of the DNA of (a).

[2234] Another embodiment is directed to fragments of a PRO1159polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 271 (SEQ ID NO:376).

[2235] In another embodiment, the invention provides isolated PRO1159polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2236] In a specific aspect, the invention provides isolated nativesequence PRO1159 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 16 to about 90 ofFIG. 272 (SEQ ID NO:377).

[2237] In another aspect, the invention concerns an isolated PRO1159polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377).

[2238] In a further aspect, the invention concerns an isolated PRO1159polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377).

[2239] In yet another aspect, the invention concerns an isolated PRO1159polypeptide, comprising the sequence of amino acid residues 1 or about16 to about 90, inclusive of FIG. 272 (SEQ ID NO:377), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1159antibody. Preferably, the PRO1159 fragment retains a qualitativebiological activity of a native PRO1159 polypeptide.

[2240] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1159 polypeptide havingthe sequence of amino acid residues from about 1 or about 16 to about90, inclusive of FIG. 272 (SEQ ID NO:377), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2241] 119. PRO1124

[2242] A cDNA clone (DNA60629-1481) has been identified, having sequenceidentity with a chloride channel protein and lung-endothelial celladhesion molecule-1 (EAM-1) that encodes a novel polypeptide, designatedin the present application as “PRO1124.”

[2243] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1124 polypeptide.

[2244] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1124 polypeptide having the sequence of aminoacid residues from about 1 or 22 to about 919, inclusive of FIG. 274(SEQ ID NO:379), or (b) the complement of the DNA molecule of (a). Asused herein, “or”, i.e., 1 or 22 and 25 or 88, is used to describe twoalternative embodiments. For example, the invention includes amino acids1 through 919 and in an alternative embodiment, provides amino acids 22through 919, etc.

[2245] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1124 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 25 or 88and about 2781, inclusive, of FIG. 273 (SEQ ID NO:378). In anotheraspect, the invention concerns an isolated nucleic acid moleculehybridizing to the complement of the nucleic acid of SEQ ID NO:378.Preferably, hybridization occurs under stringent hybridization and washconditions.

[2246] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 209979 (DNA60629-1481), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 209979 (DNA60629-1481).

[2247] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 or 22 to about 919, inclusive of FIG.274 (SEQ ID NO:379), or the complement of the DNA of (a).

[2248] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1124 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The cytoplasmic end can be excluded as well. The signal peptide has beententatively identified as extending from amino acid position 1 to aboutamino acid position 21 in the sequence of FIG. 274 (SEQ ID NO:379). Thetransmembrane domains have been tentatively identified as extending fromabout amino acid position 284 to about amino acid position 300 and fromabout amino acid position 617 to about amino acid position 633 in theamino acid sequence (FIG. 274, SEQ ID NO:379).

[2249] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or 22 to about 919, inclusive of FIG. 274 (SEQ ID NO:379), or (b) thecomplement of the DNA of (a).

[2250] In another embodiment, the invention provides isolated PRO1124polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2251] In a specific aspect, the invention provides isolated nativesequence PRO1124 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 or 22 through 919 of FIG. 274 (SEQID NO:379).

[2252] In another aspect, the invention concerns an isolated PRO1124polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or 22 to about 919, inclusive of FIG. 274 (SEQ ID NO:379).

[2253] In a further aspect, the invention concerns an isolated PRO1124polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 or 22to 919 of FIG. 274 (SEQ ID NO:379).

[2254] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1124 polypeptide havingthe sequence of amino acid residues from about 1 or 22 to about 919,inclusive of FIG. 274 (SEQ ID NO:379), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2255] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1124 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1124 antibody.

[2256] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1124 polypeptide, bycontacting the native PRO1124 polypeptide with a candidate molecule andmonitoring an activity mediated by said polypeptide.

[2257] In a still further embodiment, the invention concerns acomposition comprising a PRO1124 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2258] 120. PRO1287

[2259] A cDNA clone (DNA61755-1554) has been identified, having homologyto nucleic acid encoding fringe protein, that encodes a novelpolypeptide, designated in the present application as “PRO1287”.

[2260] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1287 polypeptide.

[2261] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1287 polypeptide having the sequence of aminoacid residues from about 1 or about 28 to about 532, inclusive of FIG.276 (SEQ ID NO:381), or (b) the complement of the DNA molecule of (a).

[2262] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1287 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 655 orabout 736 and about 2250, inclusive, of FIG. 275 (SEQ ID NO:380).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2263] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203112 (DNA61755-1554) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203112 (DNA61755-1554).

[2264] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 28 to about 532, inclusive of FIG. 276(SEQ ID NO:381), or (b) the complement of the DNA of (a).

[2265] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 100 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1287 polypeptide having the sequence of aminoacid residues from 1 or about 28 to about 532, inclusive of FIG. 276(SEQ ID NO:381), or (b) the complement of the DNA molecule of (a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2266] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1287 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 27 in the sequence of FIG.276 (SEQ ID NO:381).

[2267] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381), or (b)the complement of the DNA of (a).

[2268] Another embodiment is directed to fragments of a PRO1287polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 275 (SEQ ID NO:380).

[2269] In another embodiment, the invention provides isolated PRO1287polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2270] In a specific aspect, the invention provides isolated nativesequence PRO1287 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 28 to about 532 ofFIG. 276 (SEQ ID NO:381).

[2271] In another aspect, the invention concerns an isolated PRO1287polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381).

[2272] In a further aspect, the invention concerns an isolated PRO1287polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381).

[2273] In yet another aspect, the invention concerns an isolated PRO1287polypeptide, comprising the sequence of amino acid residues 1 or about28 to about 532, inclusive of FIG. 276 (SEQ ID NO:381), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1287antibody. Preferably, the PRO1287 fragment retains a qualitativebiological activity of a native PRO1287 polypeptide.

[2274] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1287 polypeptide havingthe sequence of amino acid residues from about 1 or about 28 to about532, inclusive of FIG. 276 (SEQ ID NO:381), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2275] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1287 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1287 antibody.

[2276] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1287 polypeptide bycontacting the native PRO1287 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2277] In a still further embodiment, the invention concerns acomposition comprising a PRO1287 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2278] 121. PRO1312

[2279] A cDNA clone (DNA61873-1574) has been identified that encodes anovel transmembrane polypeptide designated in the present application as“PRO1312”.

[2280] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1312 polypeptide.

[2281] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1312 polypeptide having the sequence of aminoacid residues from about 15 to about 212, inclusive of FIG. 278 (SEQ IDNO:387), or (b) the complement of the DNA molecule of (a).

[2282] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1312 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 49 andabout 642, inclusive, of FIG. 277 (SEQ ID NO:386). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2283] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203132 (DNA61873-1574), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203132 (DNA61873-1574).

[2284] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 15 to about 212, inclusive of FIG. 278(SEQ ID NO:387), or the complement of the DNA of (a).

[2285] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1312 polypeptide having the sequence of amino acid residues fromabout 15 to about 212, inclusive of FIG. 278 (SEQ ID NO:387), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2286] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1312 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 14 in thesequence of FIG. 278 (SEQ ID NO:387). The transmembrane domain has beententatively identified as extending from about amino acid position 141to about amino acid position 160 in the PRO1312 amino acid sequence(FIG. 278, SEQ ID NO:387).

[2287] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 15to about 212, inclusive of FIG. 278 (SEQ ID NO:387), or (b) thecomplement of the DNA of (a).

[2288] Another embodiment is directed to fragments of a PRO1312polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2289] In another embodiment, the invention provides isolated PRO1312polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2290] In a specific aspect, the invention provides isolated nativesequence PRO1312 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 15 to 212 of FIG. 278 (SEQ ID NO:387).

[2291] In another aspect, the invention concerns an isolated PRO1312polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues15 to about 212, inclusive of FIG. 278 (SEQ ID NO:387).

[2292] In a further aspect, the invention concerns an isolated PRO1312polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 15 to212 of FIG. 278 (SEQ ID NO:387).

[2293] In yet another aspect, the invention concerns an isolated PRO1312polypeptide, comprising the sequence of amino acid residues 15 to about212, inclusive of FIG. 278 (SEQ ID NO:387), or a fragment thereofsufficient to provide a binding site for an anti-PRO1312 antibody.Preferably, the PRO1312 fragment retains a qualitative biologicalactivity of a native PRO1312 polypeptide.

[2294] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1312 polypeptide havingthe sequence of amino acid residues from about 15 to about 212,inclusive of FIG. 278 (SEQ ID NO:387), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2295] 122. PRO1192

[2296] A cDNA clone (DNA62814-1521) has been identified that encodes anovel polypeptide having homology to myelin P0 protein and designated inthe present application as “PRO1192.”

[2297] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1192 polypeptide.

[2298] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1192 polypeptide having the sequence of aminoacid residues from about 22 to about 215, inclusive of FIG. 280 (SEQ IDNO:389), or (b) the complement of the DNA molecule of (a).

[2299] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1192 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 184 andabout 764, inclusive, of FIG. 279 (SEQ ID NO:388). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2300] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203093 (DNA62814-1521), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203093 (DNA62814-1521).

[2301] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 22 to about 215, inclusive of FIG. 280(SEQ ID NO:389), or the complement of the DNA of (a).

[2302] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1192 polypeptide having the sequence of amino acid residues fromabout 22 to about 215, inclusive of FIG. 280 (SEQ ID NO:389), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2303] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1192 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 21 in thesequence of FIG. 280 (SEQ ID NO:389). The transmembrane domain has beententatively identified as extending from about amino acid position 153through about amino acid position 176 in the PRO1192 amino acid sequence(FIG. 280, SEQ ID NO:389).

[2304] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 215, inclusive of FIG. 280 (SEQ ID NO:389), or (b) thecomplement of the DNA of (a).

[2305] Another embodiment is directed to fragments of a PRO1192polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2306] In another embodiment, the invention provides isolated PRO1192polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2307] In a specific aspect, the invention provides isolated nativesequence PRO1192 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 22 to 215 of FIG. 280 (SEQ ID NO:389).

[2308] In another aspect, the invention concerns an isolated PRO1192polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 215, inclusive of FIG. 280 (SEQ ID NO:389).

[2309] In a further aspect, the invention concerns an isolated PRO1192polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22 to215 of FIG. 280 (SEQ ID NO:389).

[2310] In yet another aspect, the invention concerns an isolated PRO1192polypeptide, comprising the sequence of amino acid residues 22 to about215, inclusive of FIG. 280 (SEQ ID NO:389), or a fragment thereofsufficient to provide a binding site for an anti-PRO1192 antibody.Preferably, the PRO1192 fragment retains a qualitative biologicalactivity of a native PRO1192 polypeptide.

[2311] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1192 polypeptide havingthe sequence of amino acid residues from about 22 to about 215,inclusive of FIG. 280 (SEQ ID NO:389), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2312] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1192 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1192 antibody.

[2313] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1192 polypeptide, bycontacting the native PRO1192 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2314] In a still further embodiment, the invention concerns acomposition comprising a PRO1192 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2315] 123. PRO1160

[2316] A cDNA clone (DNA62872-1509) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1160”.

[2317] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1160 polypeptide.

[2318] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1160 polypeptide having the sequence of aminoacid residues from about 1 or about 20 to about 90, inclusive of FIG.282 (SEQ ID NO:394), or (b) the complement of the DNA molecule of (a).

[2319] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1160 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 40 orabout 97 and about 309, inclusive, of FIG. 282 (SEQ ID NO:394).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2320] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203100 (DNA62872-1509) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203100 (DNA62872-1509).

[2321] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 20 to about 90, inclusive of FIG. 282(SEQ ID NO:394), or (b) the complement of the DNA of (a).

[2322] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 100 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1160 polypeptide having the sequence of aminoacid residues from 1 or about 20 to about 90, inclusive of FIG. 282 (SEQID NO:394), or (b) the complement of the DNA molecule of (a), and, ifthe DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2323] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1160 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 19 in the sequence of FIG.282 (SEQ ID NO:394).

[2324] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394), or (b)the complement of the DNA of (a).

[2325] Another embodiment is directed to fragments of a PRO1160polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 281 (SEQ ID NO:393).

[2326] In another embodiment, the invention provides isolated PRO1160polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2327] In a specific aspect, the invention provides isolated nativesequence PRO1160 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 20 to about 90 ofFIG. 282 (SEQ ID NO:394).

[2328] In another aspect, the invention concerns an isolated PRO1160polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394).

[2329] In a further aspect, the invention concerns an isolated PRO1160polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394).

[2330] In yet another aspect, the invention concerns an isolated PRO1160polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 90, inclusive of FIG. 282 (SEQ ID NO:394), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1160antibody. Preferably, the PRO1160 fragment retains a qualitativebiological activity of a native PRO1160 polypeptide.

[2331] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1160 polypeptide havingthe sequence of amino acid residues from about 1 or about 20 to about90, inclusive of FIG. 282 (SEQ ID NO:394), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2332] 124. PRO1187

[2333] A cDNA clone (DNA62876-1517) has been identified that encodes anovel polypeptide having sequence identity with endo-beta-1,4-xylanaseand designated in the present application as “PRO1187.”

[2334] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1187 polypeptide.

[2335] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1187 polypeptide having the sequence of aminoacid residues from about 18 to about 120, inclusive of FIG. 284 (SEQ IDNO:399), or (b) the complement of the DNA molecule of (a).

[2336] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1187 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 172 andabout 480, inclusive, of FIG. 283 (SEQ ID NO:398). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2337] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203095 (DNA62876-1517), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203095 (DNA62876-1517).

[2338] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 18 to about 120, inclusive of FIG. 284(SEQ ID NO:399), or the complement of the DNA of (a).

[2339] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1187 polypeptide having the sequence of amino acidresidues from about 18 to about 120, inclusive of FIG. 284 (SEQ IDNO:399), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2340] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 18to about 120, inclusive of FIG. 284 (SEQ ID NO:399), or (b) thecomplement of the DNA of (a).

[2341] Another embodiment is directed to fragments of a PRO1187polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[2342] In another embodiment, the invention provides isolated PRO1187polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2343] In a specific aspect, the invention provides isolated nativesequence PRO1187 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 18 through 120 of FIG. 284 (SEQ IDNO:399).

[2344] In another aspect, the invention concerns an isolated PRO1187polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues18 to about 120, inclusive of FIG. 284 (SEQ ID NO:399).

[2345] In a further aspect, the invention concerns an isolated PRO1187polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 18through 120 of FIG. 284 (SEQ ID NO:399).

[2346] In yet another aspect, the invention concerns an isolated PRO1187polypeptide, comprising the sequence of amino acid residues 18 to about120, inclusive of FIG. 284 (SEQ ID NO:399), or a fragment thereofsufficient to provide a binding site for an anti-PRO1187 antibody.Preferably, the PRO1187 fragment retains a qualitative biologicalactivity of a native PRO1187 polypeptide.

[2347] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1187 polypeptide havingthe sequence of amino acid residues from about 18 to about 120,inclusive of FIG. 284 (SEQ ID NO:399), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2348] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1187 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1187 antibody.

[2349] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1187 polypeptide, bycontacting the native PRO1187 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2350] In a still further embodiment, the invention concerns acomposition comprising a PRO1187 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2351] 125. PRO1185

[2352] A cDNA clone (DNA62881-1515) has been identified that encodes anovel polypeptide having sequence identity to a glucose repressionregulatory protein, tup1, and designated in the present application as“PRO1185.”

[2353] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1185 polypeptide.

[2354] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1185 polypeptide having the sequence of aminoacid residues from about 22 to about 198, inclusive of FIG. 286 (SEQ IDNO:401), or (b) the complement of the DNA molecule of (a).

[2355] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1185 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 67 andabout 597, inclusive, of FIG. 285 (SEQ ID NO:400). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2356] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203096 (DNA62881-1515), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203096 (DNA62881-1515).

[2357] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 22 to about 198, inclusive of FIG. 286(SEQ ID NO:401), or the complement of the DNA of (a).

[2358] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides nucleotides and produced by hybridizing atest DNA molecule under stringent conditions with (a) a DNA moleculeencoding a PRO1185 polypeptide having the sequence of amino acidresidues from about 22 to about 198, inclusive of FIG. 286 (SEQ IDNO:401), or (b) the complement of the DNA molecule of (a), and, if theDNA molecule has at least about an 80% sequence identity, preferably atleast about an 85% sequence identity, more preferably at least about a90% sequence identity, most preferably at least about a 95% sequenceidentity to (a) or (b), isolating the test DNA molecule.

[2359] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 22to about 198, inclusive of FIG. 286 (SEQ ID NO:401), or (b) thecomplement of the DNA of (a).

[2360] Another embodiment is directed to fragments of a PRO1185polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[2361] In another embodiment, the invention provides isolated PRO1185polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2362] In a specific aspect, the invention provides isolated nativesequence PRO1185 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 22 through 198 of FIG. 286 (SEQ IDNO:401).

[2363] In another aspect, the invention concerns an isolated PRO1185polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues22 to about 198, inclusive of FIG. 286 (SEQ ID NO:401).

[2364] In a further aspect, the invention concerns an isolated PRO1185polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 22through 198 of FIG. 286 (SEQ ID NO:401).

[2365] In yet another aspect, the invention concerns an isolated PRO1185polypeptide, comprising the sequence of amino acid residues 22 to about198, inclusive of FIG. 286 (SEQ ID NO:401), or a fragment thereofsufficient to provide a binding site for an anti-PRO1185 antibody.Preferably, the PRO1185 fragment retains a qualitative biologicalactivity of a native PRO1185 polypeptide.

[2366] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1185 polypeptide havingthe sequence of amino acid residues from about 22 to about 198,inclusive of FIG. 286 (SEQ ID NO:401), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2367] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1185 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1185 antibody.

[2368] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1185 polypeptide, bycontacting the native PRO1185 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2369] In a still further embodiment, the invention concerns acomposition comprising a PRO1185 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2370] 126. PRO1345

[2371] A cDNA clone (DNA64852-1589) has been identified, having homologyto nucleic acid encoding tetranectin protein that encodes a novelpolypeptide, designated in the present application as “PRO1345”.

[2372] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1345 polypeptide.

[2373] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1345 polypeptide having the sequence of aminoacid residues from about 1 or about 32 to about 206, inclusive of FIG.288 (SEQ ID NO:403), or (b) the complement of the DNA molecule of (a).

[2374] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1345 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 7 orabout 100 and about 624, inclusive, of FIG. 287 (SEQ ID NO:402).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2375] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203127 (DNA64852-1589) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203127 (DNA64852-1589).

[2376] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 32 to about 206, inclusive of FIG. 288(SEQ ID NO:403), or (b) the complement of the DNA of (a).

[2377] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 100 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1345 polypeptide having the sequence of aminoacid residues from 1 or about 32 to about 206, inclusive of FIG. 288(SEQ ID NO:403), or (b) the complement of the DNA molecule of (a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2378] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1345 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 or amino acid 10 to about amino acid position 31 in thesequence of FIG. 288 (SEQ ID NO:403).

[2379] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403), or (b)the complement of the DNA of (a).

[2380] Another embodiment is directed to fragments of a PRO1345polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 287 (SEQ ID NO:402).

[2381] In another embodiment, the invention provides isolated PRO1345polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2382] In a specific aspect, the invention provides isolated nativesequence PRO1345 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 32 to about 206 ofFIG. 288 (SEQ ID NO:403).

[2383] In another aspect, the invention concerns an isolated PRO1345polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403).

[2384] In a further aspect, the invention concerns an isolated PRO1345polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403).

[2385] In yet another aspect, the invention concerns an isolated PRO1345polypeptide, comprising the sequence of amino acid residues 1 or about32 to about 206, inclusive of FIG. 288 (SEQ ID NO:403), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1345antibody. Preferably, the PRO1345 fragment retains a qualitativebiological activity of a native PRO1345 polypeptide.

[2386] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1345 polypeptide havingthe sequence of amino acid residues from about 1 or about 32 to about206, inclusive of FIG. 288 (SEQ ID NO:403), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2387] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1345 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1345 antibody.

[2388] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1345 polypeptide bycontacting the native PRO1345 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2389] In a still further embodiment, the invention concerns acomposition comprising a PRO1345 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2390] 127. PRO1245

[2391] A cDNA clone (DNA64884-1527) has been identified that encodes anovel secreted polypeptide designated in the present application as“PRO1245.”

[2392] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1245 polypeptide.

[2393] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1245 polypeptide having the sequence of aminoacid residues from about 19 to about 104, inclusive of FIG. 290 (SEQ IDNO:408), or (b) the complement of the DNA molecule of (a).

[2394] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1245 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 133 andabout 390, inclusive, of FIG. 289 (SEQ ID NO:407). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2395] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203155 (DNA64884-1245), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203155 (DNA64884-1245).

[2396] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 19 to about 104, inclusive of FIG. 290(SEQ ID NO:408), or the complement of the DNA of (a).

[2397] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1245 polypeptide having the sequence of amino acid residues fromabout 19 to about 104, inclusive of FIG. 290 (SEQ ID NO:408), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2398] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1245 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from amino acidposition 1 through about amino acid position 18 in the sequence of FIG.290 (SEQ ID NO:408).

[2399] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 104, inclusive of FIG. 290 (SEQ ID NO:408), or (b) thecomplement of the DNA of (a).

[2400] Another embodiment is directed to fragments of a PRO1245polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2401] In another embodiment, the invention provides isolated PRO1245polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2402] In a specific aspect, the invention provides isolated nativesequence PRO1245 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 19 to 104 of FIG. 290 (SEQ ID NO:408).

[2403] In another aspect, the invention concerns an isolated PRO1245polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 104, inclusive of FIG. 290 (SEQ ID NO:408).

[2404] In a further aspect, the invention concerns an isolated PRO1245polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19 to104 of FIG. 290 (SEQ ID NO:408).

[2405] In yet another aspect, the invention concerns an isolated PRO1245polypeptide, comprising the sequence of amino acid residues 19 to about104, inclusive of FIG. 290 (SEQ ID NO:408), or a fragment thereofsufficient to provide a binding site for an anti-PRO1245 antibody.Preferably, the PRO1245 fragment retains a qualitative biologicalactivity of a native PRO1245 polypeptide.

[2406] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1245 polypeptide havingthe sequence of amino acid residues from about 19 to about 104,inclusive of FIG. 290 (SEQ ID NO:408), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2407] 128. PRO1358

[2408] A cDNA clone (DNA64890-1612) has been identified that encodes anovel polypeptide having sequence identity with RASP-1 and designated inthe present application as “PRO1358.”

[2409] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1358 polypeptide.

[2410] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1358 polypeptide having the sequence of aminoacid residues from about 19 to about 444, inclusive of FIG. 292 (SEQ IDNO:410), or (b) the complement of the DNA molecule of (a).

[2411] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1358 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 140 andabout 1417, inclusive, of FIG. 292 (SEQ ID NO:410). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2412] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203131 (DNA64890-1612), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203131 (DNA64890-1612).

[2413] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 19 to about 444, inclusive of FIG. 292(SEQ ID NO:410), or the complement of the DNA of (a).

[2414] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1358 polypeptide having the sequence of amino acid residues fromabout 19 to about 444, inclusive of FIG. 292 (SEQ ID NO:410), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2415] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 19to about 444, inclusive of FIG. 292 (SEQ ID NO:410), or (b) thecomplement of the DNA of (a).

[2416] Another embodiment is directed to fragments of a PRO1358polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 80 nucleotides to about 120nucleotides in length.

[2417] In another embodiment, the invention provides isolated PRO1358polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2418] In a specific aspect, the invention provides isolated nativesequence PRO1358 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 19 through 444 of FIG. 292 (SEQ IDNO:410).

[2419] In another aspect, the invention concerns an isolated PRO1358polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues19 to about 444, inclusive of FIG. 292 (SEQ ID NO:410).

[2420] In a further aspect, the invention concerns an isolated PRO1358polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 19through 444 of FIG. 292 (SEQ ID NO:410).

[2421] In yet another aspect, the invention concerns an isolated PRO1358polypeptide, comprising the sequence of amino acid residues 19 to about444, inclusive of FIG. 292 (SEQ ID NO:410), or a fragment thereofsufficient to provide a binding site for an anti-PRO1358 antibodyspecific therefore. Preferably, the PRO1358 fragment retains aqualitative biological activity of a native PRO1358 polypeptide.

[2422] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1358 polypeptide havingthe sequence of amino acid residues from about 19 to about 444,inclusive of FIG. 292 (SEQ ID NO:410), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2423] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1358 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1358 antibody.

[2424] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1358 polypeptide, bycontacting the native PRO1358 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2425] In a still further embodiment, the invention concerns acomposition comprising a PRO1358 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2426] 129. PRO1195

[2427] A cDNA clone (DNA65412-1523) has been identified that encodes anovel polypeptide having sequence identity with a mouse proline richacidic protein and designated in the present application as “PRO1195.”

[2428] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1195 polypeptide.

[2429] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1195 polypeptide having the sequence of aminoacid residues from about 23 to about 151, inclusive of FIG. 294 (SEQ IDNO:412), or (b) the complement of the DNA molecule of (a).

[2430] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1195 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 124 andabout 510, inclusive, of FIG. 293 (SEQ ID NO:411). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2431] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203094 (DNA65412-1523), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203094 (DNA65412-1523).

[2432] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 23 to about 151, inclusive of FIG. 294(SEQ ID NO:412), or the complement of the DNA of (a).

[2433] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1195 polypeptide having the sequence of amino acid residues fromabout 23 to about 151, inclusive of FIG. 294 (SEQ ID NO:412), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2434] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 23to about 151, inclusive of FIG. 294 (SEQ ID NO:412), or (b) thecomplement of the DNA of (a).

[2435] Another embodiment is directed to fragments of a PRO1195polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 through about 80nucleotides in length, preferably from about 20 through about 60nucleotides in length, more preferably from about 20 through about 50nucleotides in length, and most preferably from about 20 through about40 nucleotides in length.

[2436] In another embodiment, the invention provides isolated PRO1195polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2437] In a specific aspect, the invention provides isolated nativesequence PRO1195 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 23 through 151 of FIG. 294 (SEQ IDNO:412).

[2438] In another aspect, the invention concerns an isolated PRO1195polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues23 to about 151, inclusive of FIG. 294 (SEQ ID NO:412).

[2439] In a further aspect, the invention concerns an isolated PRO1195polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 23through 151 of FIG. 294 (SEQ ID NO:412).

[2440] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1195 polypeptide havingthe sequence of amino acid residues from about 23 to about 151,inclusive of FIG. 294 (SEQ ID NO:412), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2441] In yet another embodiment, the invention concerns agonists andantagonists of the a native PRO1195 polypeptide. In a particularembodiment, the agonist or antagonist is an anti-PRO1195 antibody.

[2442] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1195 polypeptide, bycontacting the native PRO1195 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2443] In a still further embodiment, the invention concerns acomposition comprising a PRO1195 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2444] 130. PRO1270

[2445] A cDNA clone (DNA66308-1537) has been identified, having homologyto nucleic acid encoding a lectin protein, that encodes a novelpolypeptide, designated in the present application as “PRO1270”.

[2446] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1270 polypeptide.

[2447] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1270 polypeptide having the sequence of aminoacid residues from about 1 or about 17 to about 313, inclusive of FIG.296 (SEQ ID NO:414), or (b) the complement of the DNA molecule of (a).

[2448] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1270 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 103 orabout 151 and about 1041, inclusive, of FIG. 295 (SEQ ID NO:413).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2449] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203159 (DNA66308-1537) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203159 (DNA66308-1537).

[2450] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 17 to about 313, inclusive of FIG. 296(SEQ ID NO:414), or (b) the complement of the DNA of (a).

[2451] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 285 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1270 polypeptide having the sequence of aminoacid residues from 1 or about 17 to about 313, inclusive of FIG. 296(SEQ ID NO:414), or (b) the complement of the DNA molecule of(a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2452] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1270 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 16 in the sequence of FIG.296 (SEQ ID NO:414).

[2453] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414), or (b)the complement of the DNA of (a).

[2454] Another embodiment is directed to fragments of a PRO1270polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 295 (SEQ ID NO:413).

[2455] In another embodiment, the invention provides isolated PRO1270polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2456] In a specific aspect, the invention provides isolated nativesequence PRO1270 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 17 to about 313 ofFIG. 296 (SEQ ID NO:414).

[2457] In another aspect, the invention concerns an isolated PRO1270polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414).

[2458] In a further aspect, the invention concerns an isolated PRO1270polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414).

[2459] In yet another aspect, the invention concerns an isolated PRO1270polypeptide, comprising the sequence of amino acid residues 1 or about17 to about 313, inclusive of FIG. 296 (SEQ ID NO:414), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1270antibody. Preferably, the PRO1270 fragment retains a qualitativebiological activity of a native PRO1270 polypeptide.

[2460] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1270 polypeptide havingthe sequence of amino acid residues from about 1 or about 17 to about313, inclusive of FIG. 296 (SEQ ID NO:414), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2461] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1270 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1270 antibody.

[2462] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1270 polypeptide bycontacting the native PRO1270 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2463] In a still further embodiment, the invention concerns acomposition comprising a PRO1270 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2464] 131. PRO1271

[2465] A cDNA clone (DNA66309-1538) has been identified that encodes anovel polypeptide having serine and threonine rich regions designated inthe present application as “PRO1271” polypeptides.

[2466] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1271 polypeptide.

[2467] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1271 polypeptide having the sequence of aminoacid residues from about 32 to about 208, inclusive of FIG. 298 (SEQ IDNO:416), or (b) the complement of the DNA molecule of (a).

[2468] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1271 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 187 andabout 717, inclusive, of FIG. 297 (SEQ ID NO:415). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2469] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203235 (DNA66309-1538), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203235 (DNA66309-1538).

[2470] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 32 to about 208, inclusive of FIG. 298(SEQ ID NO:416), or the complement of the DNA of (a).

[2471] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1271 polypeptide having the sequence of amino acid residues fromabout 32 to about 208, inclusive of FIG. 298 (SEQ ID NO:416), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2472] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1271 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e. transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromamino acid position 1 through about amino acid position 31 in thesequence of FIG. 298 (SEQ ID NO:416). The transmembrane domain has beententatively identified as extending from about amino acid position 166through about amino acid position 187 in the PRO1271 amino acid sequence(FIG. 298, SEQ ID NO:416).

[2473] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 32to about 208, inclusive of FIG. 298 (SEQ ID NO:416), or (b) thecomplement of the DNA of (a).

[2474] Another embodiment is directed to fragments of a PRO1271polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2475] In another embodiment, the invention provides isolated PRO1271polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2476] In a specific aspect, the invention provides isolated nativesequence PRO1271 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 32 through 208 of FIG. 298 (SEQ IDNO:416).

[2477] In another aspect, the invention concerns an isolated PRO1271polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues32 to about 208, inclusive of FIG. 298 (SEQ ID NO:416).

[2478] In a further aspect, the invention concerns an isolated PRO1271polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 32through 208 of FIG. 298 (SEQ ID NO:416).

[2479] In yet another aspect, the invention concerns an isolated PRO1271polypeptide, comprising the sequence of amino acid residues 32 to about208, inclusive of FIG. 298 (SEQ ID NO:416), or a fragment thereofsufficient to provide a binding site for an anti-PRO1271 antibody.Preferably, the PRO1271 fragment retains a qualitative biologicalactivity of a native PRO1271 polypeptide.

[2480] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1271 polypeptide havingthe sequence of amino acid residues from about 32 to about 208,inclusive of FIG. 298 (SEQ ID NO:416), or (b) the complement of the DNAmolecule of (a), and if the test DNA molecule has at least about an 80%sequence identity, preferably at least about an 85% sequence identity,more preferably at least about a 90% sequence identity, most preferablyat least about a 95% sequence identity to (a) or (b), (ii) culturing ahost cell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2481] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1271 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1271 antibody.

[2482] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1271 polypeptide, bycontacting the native PRO1271 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2483] In a still further embodiment, the invention concerns acomposition comprising a PRO1271 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2484] 132. PRO1375

[2485] A cDNA clone (DNA67004-1614) has been identified that encodes anovel polypeptide having sequence identity with PUT2 and designated inthe present application as “PRO1375.”

[2486] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1375 polypeptide.

[2487] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1375 polypeptide having the sequence of aminoacid residues from about 1 to about 198, inclusive of FIG. 300 (SEQ IDNO:418), or (b) the complement of the DNA molecule of (a).

[2488] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1375 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 104 andabout 697, inclusive, of FIG. 299 (SEQ ID NO:417). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2489] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203115 (DNA67004-1614), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203115 (DNA67004-1614).

[2490] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 198, inclusive of FIG. 300(SEQ ID NO:418), or the complement of the DNA of (a).

[2491] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1375 polypeptide having the sequence of amino acid residues fromabout 1 to about 198, inclusive of FIG. 300 (SEQ ID NO:418), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2492] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1375 polypeptide in itssoluble form, i.e. transmembrane domains deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The transmembrane domains have been tentatively identified as at aboutamino acid positions 11-28 (type II) and 103-125 of SEQ ID NO:418.

[2493] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 198, inclusive of FIG. 300 (SEQ ID NO:418), or (b) thecomplement of the DNA of (a).

[2494] Another embodiment is directed to fragments of a PRO1375polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2495] In another embodiment, the invention provides isolated PRO1375polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2496] In a specific aspect, the invention provides isolated nativesequence PRO1375 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 through 198 of FIG. 300 (SEQ IDNO:418).

[2497] In another aspect, the invention concerns an isolated PRO1375polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 198, inclusive of FIG. 300 (SEQ ID NO:418).

[2498] In a further aspect, the invention concerns an isolated PRO1375polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1through 198 of FIG. 300 (SEQ ID NO:418).

[2499] In yet another aspect, the invention concerns an isolated PRO1375polypeptide, comprising the sequence of amino acid residues 1 to about198, inclusive of FIG. 300 (SEQ ID NO:418), or a fragment thereofsufficient to provide a binding site for an anti-PRO1375 antibody.Preferably, the PRO1375 fragment retains a qualitative biologicalactivity of a native PRO1375 polypeptide.

[2500] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1375 polypeptide havingthe sequence of amino acid residues from about 1 to about 198, inclusiveof FIG. 300 (SEQ ID NO:418), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2501] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1375 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1375 antibody.

[2502] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1375 polypeptide, bycontacting the native PRO1375 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2503] In a still further embodiment, the invention concerns acomposition comprising a PRO1375 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2504] 133. PRO1385

[2505] A cDNA clone (DNA68869-1610) has been identified that encodes anovel secreted polypeptide, designated in the present application as“PRO1385”.

[2506] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1385 polypeptide.

[2507] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1385 polypeptide having the sequence of aminoacid residues from about 1 or about 29 to about 128, inclusive of FIG.302 (SEQ ID NO:420), or (b) the complement of the DNA molecule of (a).

[2508] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1385 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 26 orabout 110 and about 409, inclusive, of FIG. 301 (SEQ ID NO:419).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2509] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203164 (DNA68869-1610) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203164 (DNA68869-1610).

[2510] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 29 to about 128, inclusive of FIG. 302(SEQ ID NO:420), or (b) the complement of the DNA of (a).

[2511] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 245 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1385 polypeptide having the sequence of aminoacid residues from 1 or about 29 to about 128, inclusive of FIG. 302(SEQ ID NO:420), or (b) the complement of the DNA molecule of (a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2512] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1385 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,or is complementary to such encoding nucleic acid molecule. The signalpeptide has been tentatively identified as extending from about aminoacid position 1 to about amino acid position 28 in the sequence of FIG.302 (SEQ ID NO:420).

[2513] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420), or (b)the complement of the DNA of (a).

[2514] Another embodiment is directed to fragments of a PRO1385polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length and mostpreferably from about 20 to about 40 nucleotides in length and may bederived from the nucleotide sequence shown in FIG. 301 (SEQ ID NO:419).

[2515] In another embodiment, the invention provides isolated PRO1385polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2516] In a specific aspect, the invention provides isolated nativesequence PRO1385 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 29 to about 128 ofFIG. 302 (SEQ ID NO:420).

[2517] In another aspect, the invention concerns an isolated PRO1385polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420).

[2518] In a further aspect, the invention concerns an isolated PRO1385polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420).

[2519] In yet another aspect, the invention concerns an isolated PRO1385polypeptide, comprising the sequence of amino acid residues 1 or about29 to about 128, inclusive of FIG. 302 (SEQ ID NO:420), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1385antibody. Preferably, the PRO1385 fragment retains a qualitativebiological activity of a native PRO1385 polypeptide.

[2520] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1385 polypeptide havingthe sequence of amino acid residues from about 1 or about 29 to about128, inclusive of FIG. 302 (SEQ ID NO:420), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2521] 134. PRO1387

[2522] A cDNA clone (DNA68872-1620) has been identified, having homologyto nucleic acid encoding myelin, that encodes a novel polypeptide,designated in the present application as “PRO1387”.

[2523] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1387 polypeptide.

[2524] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1387 polypeptide having the sequence of aminoacid residues from about 1 or about 20 to about 394, inclusive of FIG.304 (SEQ ID NO:422), or (b) the complement of the DNA molecule of (a).

[2525] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1387 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about nucleotides 85 orabout 142 and about 1266, inclusive, of FIG. 303 (SEQ ID NO:421).Preferably, hybridization occurs under stringent hybridization and washconditions.

[2526] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203160 (DNA68872-1620) or (b) the complement of the nucleicacid molecule of (a). In a preferred embodiment, the nucleic acidcomprises a DNA encoding the same mature polypeptide encoded by thehuman protein cDNA in ATCC Deposit No. 203160 (DNA68872-1620).

[2527] In still a further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues 1 or about 20 to about 394, inclusive of FIG. 304(SEQ ID NO:422), or (b) the complement of the DNA of (a).

[2528] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least 395 nucleotides and produced byhybridizing a test DNA molecule under stringent conditions with (a) aDNA molecule encoding a PRO1387 polypeptide having the sequence of aminoacid residues from 1 or about 20 to about 394, inclusive of FIG. 304(SEQ ID NO:422), or (b) the complement of the DNA molecule of (a), and,if the DNA molecule has at least about an 80% sequence identity,prefereably at least about an 85% sequence identity, more preferably atleast about a 90% sequence identity, most preferably at least about a95% sequence identity to (a) or (b), isolating the test DNA molecule.

[2529] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1387 polypeptide, with orwithout the N-terminal signal sequence and/or the initiating methionine,and its soluble, i.e., transmembrane domain deleted or inactivatedvariants, or is complementary to such encoding nucleic acid molecule.The signal peptide has been tentatively identified as extending fromabout amino acid position 1 to about amino acid position 19 in thesequence of FIG. 304 (SEQ ID NO:422). The transmembrane domain has beententatively identified as extending from about amino acid position 275to about amino acid position 296 in the PRO1387 amino acid sequence(FIG. 304, SEQ ID NO:422).

[2530] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1or about 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422), or (b)the complement of the DNA of (a).

[2531] Another embodiment is directed to fragments of aPRO1387-polypeptide coding sequence that may find use as hybridizationprobes. Such nucleic acid fragments are from about 20 to about 80nucleotides in length, preferably from about 20 to about 60 nucleotidesin length, more preferably from about 20 to about 50 nucleotides inlength and most preferably from about 20 to about 40 nucleotides inlength and may be derived from the nucleotide sequence shown in FIG. 303(SEQ ID NO:421).

[2532] In another embodiment, the invention provides isolated PRO1387polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2533] In a specific aspect, the invention provides isolated nativesequence PRO1387 polypeptide, which in certain embodiments, includes anamino acid sequence comprising residues 1 or about 20 to about 394 ofFIG. 304 (SEQ ID NO:422).

[2534] In another aspect, the invention concerns an isolated PRO1387polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 or about 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422).

[2535] In a further aspect, the invention concerns an isolated PRO1387polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 orabout 20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422).

[2536] In yet another aspect, the invention concerns an isolated PRO1387polypeptide, comprising the sequence of amino acid residues 1 or about20 to about 394, inclusive of FIG. 304 (SEQ ID NO:422), or a fragmentthereof sufficient to provide a binding site for an anti-PRO1387antibody. Preferably, the PRO1387 fragment retains a qualitativebiological activity of a native PRO1387 polypeptide.

[2537] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1387 polypeptide havingthe sequence of amino acid residues from about 1 or about 20 to about394, inclusive of FIG. 304 (SEQ ID NO:422), or (b) the complement of theDNA molecule of (a), and if the test DNA molecule has at least about an80% sequence identity, preferably at least about an 85% sequenceidentity, more preferably at least about a 90% sequence identity, mostpreferably at least about a 95% sequence identity to (a) or (b), (ii)culturing a host cell comprising the test DNA molecule under conditionssuitable for expression of the polypeptide, and (iii) recovering thepolypeptide from the cell culture.

[2538] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1387 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1387 antibody.

[2539] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1387 polypeptide bycontacting the native PRO1387 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2540] In a still further embodiment, the invention concerns acomposition comprising a PRO1387 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2541] 135. PRO1384

[2542] A cDNA clone, referred to herein as “DNA71159”, has beenidentified that encodes a novel polypeptide having homology to NKG2-Dprotein designated in the present application as “PRO1384”.

[2543] In one embodiment, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1384 polypeptide.

[2544] In one aspect, the isolated nucleic acid comprises DNA having atleast about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to (a) a DNAmolecule encoding a PRO1384 polypeptide having the sequence of aminoacid residues from about 1 to about 229, inclusive of FIG. 306 (SEQ IDNO:424), or (b) the complement of the DNA molecule of (a).

[2545] In another aspect, the invention concerns an isolated nucleicacid molecule encoding a PRO1384 polypeptide comprising DNA hybridizingto the complement of the nucleic acid between about residues 182 andabout 868, inclusive, of FIG. 305 (SEQ ID NO:423). Preferably,hybridization occurs under stringent hybridization and wash conditions.

[2546] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising DNA having at least about 80% sequenceidentity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to (a) a DNA molecule encoding thesame mature polypeptide encoded by the human protein cDNA in ATCCDeposit No. 203135 (DNA71159-1617), or (b) the complement of the DNAmolecule of (a). In a preferred embodiment, the nucleic acid comprises aDNA encoding the same mature polypeptide encoded by the human proteincDNA in ATCC Deposit No. 203135 (DNA71159-1617).

[2547] In a still further aspect, the invention concerns an isolatednucleic acid molecule comprising (a) DNA encoding a polypeptide havingat least about 80% sequence identity, preferably at least about 85%sequence identity, more preferably at least about 90% sequence identity,most preferably at least about 95% sequence identity to the sequence ofamino acid residues from about 1 to about 229, inclusive of FIG. 306(SEQ ID NO:424), or the complement of the DNA of (a).

[2548] In a further aspect, the invention concerns an isolated nucleicacid molecule having at least about 50 nucleotides, and preferably atleast about 100 nucleotides and produced by hybridizing a test DNAmolecule under stringent conditions with (a) a DNA molecule encoding aPRO1384 polypeptide having the sequence of amino acid residues fromabout 1 to about 229, inclusive of FIG. 306 (SEQ ID NO:424), or (b) thecomplement of the DNA molecule of (a), and, if the DNA molecule has atleast about an 80% sequence identity, preferably at least about an 85%sequence identity, more preferably at least about a 90% sequenceidentity, most preferably at least about a 95% sequence identity to (a)or (b), isolating the test DNA molecule.

[2549] In a specific aspect, the invention provides an isolated nucleicacid molecule comprising DNA encoding a PRO1384 polypeptide with itstransmembrane domain deleted or inactivated, or is complementary to suchencoding nucleic acid molecule. The transmembrane domain has beententatively identified as extending from about amino acid position 32through about amino acid position 57 in the PRO1384 amino acid sequence(FIG. 306, SEQ ID NO:424).

[2550] In another aspect, the invention concerns an isolated nucleicacid molecule comprising (a) DNA encoding a polypeptide scoring at leastabout 80% positives, preferably at least about 85% positives, morepreferably at least about 90% positives, most preferably at least about95% positives when compared with the amino acid sequence of residues 1to about 229, inclusive of FIG. 306 (SEQ ID NO:424), or (b) thecomplement of the DNA of (a).

[2551] Another embodiment is directed to fragments of a PRO1384polypeptide coding sequence that may find use as hybridization probes.Such nucleic acid fragments are from about 20 to about 80 nucleotides inlength, preferably from about 20 to about 60 nucleotides in length, morepreferably from about 20 to about 50 nucleotides in length, and mostpreferably from about 20 to about 40 nucleotides in length.

[2552] In another embodiment, the invention provides isolated PRO1384polypeptide encoded by any of the isolated nucleic acid sequenceshereinabove defined.

[2553] In a specific aspect, the invention provides isolated nativesequence PRO1384 polypeptide, which in one embodiment, includes an aminoacid sequence comprising residues 1 to 229 of FIG. 306 (SEQ ID NO:424).

[2554] In another aspect, the invention concerns an isolated PRO1384polypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 85% sequence identity, morepreferably at least about 90% sequence identity, most preferably atleast about 95% sequence identity to the sequence of amino acid residues1 to about 229, inclusive of FIG. 306 (SEQ ID NO:424).

[2555] In a further aspect, the invention concerns an isolated PRO1384polypeptide, comprising an amino acid sequence scoring at least about80% positives, preferably at least about 85% positives, more preferablyat least about 90% positives, most preferably at least about 95%positives when compared with the amino acid sequence of residues 1 to229 of FIG. 306 (SEQ ID NO:424).

[2556] In yet another aspect, the invention concerns an isolated PRO1384polypeptide, comprising the sequence of amino acid residues 1 to about229, inclusive of FIG. 306 (SEQ ID NO:424), or a fragment thereofsufficient to provide a binding site for an anti-PRO1384 antibody.Preferably, the PRO1384 fragment retains a qualitative biologicalactivity of a native PRO1384 polypeptide.

[2557] In a still further aspect, the invention provides a polypeptideproduced by (i) hybridizing a test DNA molecule under stringentconditions with (a) a DNA molecule encoding a PRO1384 polypeptide havingthe sequence of amino acid residues from about 1 to about 229, inclusiveof FIG. 306 (SEQ ID NO:424), or (b) the complement of the DNA moleculeof (a), and if the test DNA molecule has at least about an 80% sequenceidentity, preferably at least about an 85% sequence identity, morepreferably at least about a 90% sequence identity, most preferably atleast about a 95% sequence identity to (a) or (b), (ii) culturing a hostcell comprising the test DNA molecule under conditions suitable forexpression of the polypeptide, and (iii) recovering the polypeptide fromthe cell culture.

[2558] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO1384 polypeptide. In a particular embodiment,the agonist or antagonist is an anti-PRO1384 antibody.

[2559] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists of a native PRO1384 polypeptide, bycontacting the native PRO1384 polypeptide with a candidate molecule andmonitoring a biological activity mediated by said polypeptide.

[2560] In a still further embodiment, the invention concerns acomposition comprising a PRO1384 polypeptide, or an agonist orantagonist as hereinabove defined, in combination with apharmaceutically acceptable carrier.

[2561] 136. Additional Embodiments

[2562] In other embodiments of the present invention, the inventionprovides vectors comprising DNA encoding any of the herein describedpolypeptides. Host cell comprising any such vector are also provided. Byway of example, the host cells may be CHO cells, E. coli, or yeast. Aprocess for producing any of the herein described polypeptides isfurther provided and comprises culturing host cells under conditionssuitable for expression of the desired polypeptide and recovering thedesired polypeptide from the cell culture.

[2563] In other embodiments, the invention provides chimeric moleculescomprising any of the herein described polypeptides fused to aheterologous polypeptide or amino acid sequence. Example of suchchimeric molecules comprise any of the herein described polypeptidesfused to an epitope tag sequence or a Fc region of an immunoglobulin.

[2564] In another embodiment, the invention provides an antibody whichspecifically binds to any of the above or below described polypeptides.Optionally, the antibody is a monoclonal antibody, humanized antibody,antibody fragment or single-chain antibody.

[2565] In yet other embodiments, the invention provides oligonucleotideprobes useful for isolating genomic and cDNA nucleotide sequences or asantisense probes, wherein those probes may be derived from any of theabove or below described nucleotide sequences.

[2566] In other embodiments, the invention provides an isolated nucleicacid molecule comprising a nucleotide sequence that encodes a PROpolypeptide.

[2567] In one aspect, the isolated nucleic acid molecule comprises anucleotide sequence having at least about 80% sequence identity,preferably at least about 81% sequence identity, more preferably atleast about 82% sequence identity, yet more preferably at least about83% sequence identity, yet more preferably at least about 84% sequenceidentity, yet more preferably at least about 85% sequence identity, yetmore preferably at least about 86% sequence identity, yet morepreferably at least about 87% sequence identity, yet more preferably atleast about 88% sequence identity, yet more preferably at least about89% sequence identity, yet more preferably at least about 90% sequenceidentity, yet more preferably at least about 91% sequence identity, yetmore preferably at least about 92% sequence identity, yet morepreferably at least about 93% sequence identity, yet more preferably atleast about 94% sequence identity, yet more preferably at least about95% sequence identity, yet more preferably at least about 96% sequenceidentity, yet more preferably at least about 97% sequence identity, yetmore preferably at least about 98% sequence identity and yet morepreferably at least about 99% sequence identity to (a) a DNA moleculeencoding a PRO polypeptide having a fill-length amino acid sequence asdisclosed herein, an amino acid sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a transmembrane protein,with or without the signal peptide, as disclosed herein or any otherspecifically defined fragment of the full-length amino acid sequence asdisclosed herein, or (b) the complement of the DNA molecule of (a).

[2568] In other aspects, the isolated nucleic acid molecule comprises anucleotide sequence having at least about 80% sequence identity,preferably at least about 81% sequence identity, more preferably atleast about 82% sequence identity, yet more preferably at least about83% sequence identity, yet more preferably at least about 84% sequenceidentity, yet more preferably at least about 85% sequence identity, yetmore preferably at least about 86% sequence identity, yet morepreferably at least about 87% sequence identity, yet more preferably atleast about 88% sequence identity, yet more preferably at least about89% sequence identity, yet more preferably at least about 90% sequenceidentity, yet more preferably at least about 91% sequence identity, yetmore preferably at least about 92% sequence identity, yet morepreferably at least about 93% sequence identity, yet more preferably atleast about 94% sequence identity, yet more preferably at least about95% sequence identity, yet more preferably at least about 96% sequenceidentity, yet more preferably at least about 97% sequence identity, yetmore preferably at least about 98% sequence identity and yet morepreferably at least about 99% sequence identity to (a) a DNA moleculecomp rising the coding sequence of a full-length PRO polypeptide cDNA asdisclosed herein, the coding sequence of a PRO polypeptide lacking thesignal peptide as disclosed herein, the coding sequence of anextracellular domain of a transmembrane PRO polypeptide, with or withoutthe signal peptide, as disclosed herein or the coding sequence of anyother specifically defined fragment of the full-length amino acidsequence as disclosed herein, or (b) the complement of the DNA moleculeof (a).

[2569] In a further aspect, the invention concerns an isolated nucleicacid molecule comprising a nucleotide sequence having at least about 80%sequence identity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to (a) a DNAmolecule that encodes the same mature polypeptide encoded by any of thehuman protein cDNAs deposited with the ATCC as disclosed herein, or (b)the complement of the DNA molecule of (a).

[2570] Another aspect the invention provides an isolated nucleic acidmolecule comprising a nucleotide sequence encoding a PRO polypeptidewhich is either transmembrane domain-deleted or transmembranedomain-inactivated, or is complementary to such encoding nucleotidesequence, wherein the transmembrane domain(s) of such polypeptide aredisclosed herein. Therefore, soluble extracellular domains of the hereindescribed PRO polypeptides are contemplated.

[2571] Another embodiment is directed to fragments of a PRO polypeptidecoding sequence, or the complement thereof, that may find use as, forexample, hybridization probes, for encoding fragments of a PROpolypeptide that may optionally encode a polypeptide comprising abinding site for an anti-PRO antibody or as antisense oligonucleotideprobes. Such nucleic acid fragments are usually at least about 20nucleotides in length, preferably at least about 30 nucleotides inlength, more preferably at least about 40 nucleotides in length, yetmore preferably at least about 50 nucleotides in length, yet morepreferably at least about 60 nucleotides in length, yet more preferablyat least about 70 nucleotides in length, yet more preferably at leastabout 80 nucleotides in length, yet more preferably at least about 90nucleotides in length, yet more preferably at least about 100nucleotides in length, yet more preferably at least about 110nucleotides in length, yet more preferably at least about 120nucleotides in length, yet more preferably at least about 130nucleotides in length, yet more preferably at least about 140nucleotides in length, yet more preferably at least about 150nucleotides in length, yet more preferably at least about 160nucleotides in length, yet more preferably at least about 170nucleotides in length, yet more preferably at least about 180nucleotides in length, yet more preferably at least about 190nucleotides in length, yet more preferably at least about 200nucleotides in length, yet more preferably at least about 250nucleotides in length, yet more preferably at least about 300nucleotides in length, yet more preferably at least about 350nucleotides in length, yet more preferably at least about 400nucleotides in length, yet more preferably at least about 450nucleotides in length, yet more preferably at least about 500nucleotides in length, yet more preferably at least about 600nucleotides in length, yet more preferably at least about 700nucleotides in length, yet more preferably at least about 800nucleotides in length, yet more preferably at least about 900nucleotides in length and yet more preferably at least about 1000nucleotides in length, wherein in this context the term “about” meansthe referenced nucleotide sequence length plus or minus 10% of thatreferenced length. It is noted that novel fragments of a PROpolypeptide-encoding nucleotide sequence may be determined in a routinemanner by aligning the PRO polypeptide-encoding nucleotide sequence withother known nucleotide sequences using any of a number of well knownsequence alignment programs and determining which PROpolypeptide-encoding nucleotide sequence fragment(s) are novel. All ofsuch PRO polypeptide-encoding nucleotide sequences are contemplatedherein. Also contemplated are the PRO polypeptide fragments encoded bythese nucleotide molecule fragments, preferably those PRO polypeptidefragments that comprise a binding site for an anti-PRO antibody.

[2572] In another embodiment, the invention provides isolated PROpolypeptide encoded by any of the isolated nucleic acid sequenceshereinabove identified.

[2573] In a certain aspect, the invention concerns an isolated PROpolypeptide, comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to a PROpolypeptide having a full-length amino acid sequence as disclosedherein, an amino acid sequence lacking the signal peptide as disclosedherein, an extracellular domain of a transmembrane protein, with orwithout the signal peptide, as disclosed herein or any otherspecifically defined fragment of the full-length amino acid sequence asdisclosed herein.

[2574] In a further aspect, the invention concerns an isolated PROpolypeptide comprising an amino acid sequence having at least about 80%sequence identity, preferably at least about 81% sequence identity, morepreferably at least about 82% sequence identity, yet more preferably atleast about 83% sequence identity, yet more preferably at least about84% sequence identity, yet more preferably at least about 85% sequenceidentity, yet more preferably at least about 86% sequence identity, yetmore preferably at least about 87% sequence identity, yet morepreferably at least about 88% sequence identity, yet more preferably atleast about 89% sequence identity, yet more preferably at least about90% sequence identity, yet more preferably at least about 91% sequenceidentity, yet more preferably at least about 92% sequence identity, yetmore preferably at least about 93% sequence identity, yet morepreferably at least about 94% sequence identity, yet more preferably atleast about 95% sequence identity, yet more preferably at least about96% sequence identity, yet more preferably at least about 97% sequenceidentity, yet more preferably at least about 98% sequence identity andyet more preferably at least about 99% sequence identity to an aminoacid sequence encoded by any of the human protein cDNAs deposited withthe ATCC as disclosed herein.

[2575] In a further aspect, the invention concerns an isolated PROpolypeptide comprising an amino acid sequence scoring at least about 80%positives, preferably at least about 81% positives, more preferably atleast about 82% positives, yet more preferably at least about 83%positives, yet more preferably at least about 84% positives, yet morepreferably at least about 85% positives, yet more preferably at leastabout 86% positives, yet more preferably at least about 87% positives,yet more preferably at least about 88% positives, yet more preferably atleast about 89% positives, yet more preferably at least about 90%positives, yet more preferably at least about 91% positives, yet morepreferably at least about 92% positives, yet more preferably at leastabout 93% positives, yet more preferably at least about 94% positives,yet more preferably at least about 95% positives, yet more preferably atleast about 96% positives, yet more preferably at least about 97%positives, yet more preferably at least about 98% positives and yet morepreferably at least about 99% positives when compared with the aminoacid sequence of a PRO polypeptide having a full-length amino acidsequence as disclosed herein, an amino acid sequence lacking the signalpeptide as disclosed herein, an extracellular domain of a transmembraneprotein, with or without the signal peptide, as disclosed herein or anyother specifically defined fragment of the full-length amino acidsequence as disclosed herein.

[2576] In a specific aspect, the invention provides an isolated PROpolypeptide without the N-terminal signal sequence and/or the initiatingmethionine and is encoded by a nucleotide sequence that encodes such anamino acid sequence as hereinbefore described. Processes for producingthe same are also herein described, wherein those processes compriseculturing a host cell comprising a vector which comprises theappropriate encoding nucleic acid molecule under conditions suitable forexpression of the PRO polypeptide and recovering the PRO polypeptidefrom the cell culture.

[2577] Another aspect the invention provides an isolated PRO polypeptidewhich is either transmembrane domain-deleted or transmembranedomain-inactivated. Processes for producing the same are also hereindescribed, wherein those processes comprise culturing a host cellcomprising a vector which comprises the appropriate encoding nucleicacid molecule under conditions suitable for expression of the PROpolypeptide and recovering the PRO polypeptide from the cell culture.

[2578] In yet another embodiment, the invention concerns agonists andantagonists of a native PRO polypeptide as defined herein. In aparticular embodiment, the agonist or antagonist is an anti-PRO antibodyor a small molecule.

[2579] In a further embodiment, the invention concerns a method ofidentifying agonists or antagonists to a PRO polypeptide which comprisecontacting the PRO polypeptide with a candidate molecule and monitoringa biological activity mediated by said PRO polypeptide. Preferably, thePRO polypeptide is a native PRO polypeptide.

[2580] In a still further embodiment, the invention concerns acomposition of matter comprising a PRO polypeptide, or an agonist orantagonist of a PRO polypeptide as herein described, or an anti-PROantibody, in combination with a carrier. Optionally, the carrier is apharmaceutically acceptable carrier.

[2581] Another embodiment of the present invention is directed to theuse of a PRO polypeptide, or an agonist or antagonist thereof ashereinbefore described, or an anti-PRO antibody, for the preparation ofa medicament useful in the treatment of a condition which is responsiveto the PRO polypeptide, an agonist or antagonist thereof or an anti-PROantibody.

BRIEF DESCRIPTION OF THE DRAWINGS

[2582]FIG. 1 shows a nucleotide sequence (SEQ ID NO:1) of a nativesequence PRO281 (UNQ244) cDNA, wherein SEQ ID NO:1 is a clone designatedherein as “DNA16422-1209”.

[2583]FIG. 2 shows the amino acid sequence (SEQ ID NO:2) derived fromthe coding sequence of SEQ ID NO:1 shown in FIG. 1.

[2584]FIG. 3 shows a nucleotide sequence (SEQ ID NO:5) of a nativesequence PRO276 (UNQ243) cDNA, wherein SEQ ID NO:5 is a clone designatedherein as “DNA16435-1208”.

[2585]FIG. 4 shows the amino acid sequence (SEQ ID NO:6) derived fromthe coding sequence of SEQ ID NO:5 shown in FIG. 3.

[2586]FIG. 5 shows a nucleotide sequence (SEQ ID NO:7) of a nativesequence PRO189 (UNQ163) cDNA, wherein SEQ ID NO:7 is a clone designatedherein as “DNA21624-1391”.

[2587]FIG. 6 shows the amino acid sequence (SEQ ID NO:8) derived fromthe coding sequence of SEQ ID NO:7 shown in FIG. 5.

[2588]FIG. 7 shows a nucleotide sequence designated herein as DNA14187(SEQ ID NO:9).

[2589]FIG. 8 shows a nucleotide sequence (SEQ ID NO:13) of a nativesequence PRO190 (UNQ164) cDNA, wherein SEQ ID NO:13 is a clonedesignated herein as “DNA23334-1392”.

[2590]FIG. 9 shows the amino acid sequence (SEQ ID NO:14) derived fromthe coding sequence of SEQ ID NO:13 shown in FIG. 8.

[2591]FIG. 10 shows a nucleotide sequence designated herein as DNA14232(SEQ ID NO:15).

[2592]FIG. 11 shows a nucleotide sequence (SEQ ID NO:19) of a nativesequence PRO341 (UNQ300) cDNA, wherein SEQ ID NO:19 is a clonedesignated herein as “DNA26288-1239”.

[2593]FIG. 12 shows the amino acid sequence (SEQ ID NO:20) derived fromthe coding sequence of SEQ ID NO:19 shown in FIG. 11.

[2594]FIG. 13 shows a nucleotide sequence designated herein as DNA12920(SEQ ID NO:21).

[2595]FIG. 14 shows a nucleotide sequence (SEQ ID NO:22) of a nativesequence PRO180 (UNQ154) cDNA, wherein SEQ ID NO:22 is a clonedesignated herein as “DNA26843-1389”.

[2596]FIG. 15 shows the amino acid sequence (SEQ ID NO:23) derived fromthe coding sequence of SEQ ID NO:22 shown in FIG. 14.

[2597]FIG. 16 shows a nucleotide sequence designated herein as DNA12922(SEQ ID NO:24).

[2598]FIG. 17 shows a nucleotide sequence (SEQ ID NO:27) of a nativesequence PRO194 (UNQ168) cDNA, wherein SEQ ID NO:27 is a clonedesignated herein as “DNA26844-1394”.

[2599]FIG. 18 shows the amino acid sequence (SEQ ID NO:28) derived fromthe coding sequence of SEQ ID NO:27 shown in FIG. 17.

[2600]FIG. 19 shows a nucleotide sequence (SEQ ID NO:29) of a nativesequence PRO203 (UNQ177) cDNA, wherein SEQ ID NO:29 is a clonedesignated herein as “DNA30862-1396”.

[2601]FIG. 20 shows the amino acid sequence (SEQ ID NO:30) derived fromthe coding sequence of SEQ ID NO:29 shown in FIG. 19.

[2602]FIG. 21 shows a nucleotide sequence designated herein as DNA15618(SEQ ID NO:31).

[2603]FIG. 22 shows a nucleotide sequence (SEQ ID NO:32) of a nativesequence PRO290 (UNQ253) cDNA, wherein SEQ ID NO:32 is a clonedesignated herein as “DNA35680-1212”.

[2604]FIG. 23 shows the amino acid sequence (SEQ ID NO:33) derived fromthe coding sequence of SEQ ID NO:32 shown in FIG. 22.

[2605]FIG. 24 shows a nucleotide sequence (SEQ ID NO:35) of a nativesequence PRO874 (UNQ441) cDNA, wherein SEQ ID NO:35 is a clonedesignated herein as “DNA40621-1440”.

[2606]FIG. 25 shows the amino acid sequence (SEQ ID NO:36) derived fromthe coding sequence of SEQ ID NO:35 shown in FIG. 24.

[2607]FIG. 26 shows a nucleotide sequence (SEQ ID NO:40) of a nativesequence PRO710 (UNQ374) cDNA, wherein SEQ ID NO:40 is a clonedesignated herein as “DNA44161-1434”.

[2608]FIG. 27 shows the amino acid sequence (SEQ ID NO:41) derived fromthe coding sequence of SEQ ID NO:40 shown in FIG. 26.

[2609]FIG. 28 shows a nucleotide sequence designated herein as DNA38190(SEQ ID NO:42).

[2610]FIG. 29 shows a nucleotide sequence (SEQ ID NO:46) of a nativesequence PRO1151 (UNQ581) cDNA, wherein SEQ ID NO:46 is a clonedesignated herein as “DNA44694-1500”.

[2611]FIG. 30 shows the amino acid sequence (SEQ ID NO:47) derived fromthe coding sequence of SEQ ID NO:46 shown in FIG. 29.

[2612]FIG. 31 shows a nucleotide sequence (SEQ ID NO:51) of a nativesequence PRO1282 (UNQ652) cDNA, wherein SEQ ID NO:51 is a clonedesignated herein as “DNA45495-1550”.

[2613]FIG. 32 shows the amino acid sequence (SEQ ID NO:52) derived fromthe coding sequence of SEQ ID NO:51 shown in FIG. 31.

[2614]FIG. 33 shows a nucleotide sequence (SEQ ID NO:56) of a nativesequence PRO358 cDNA, wherein SEQ ID NO:56 is a clone designated hereinas “DNA47361-1154.”

[2615]FIG. 34 shows the amino acid sequence (SEQ ID NO:57) derived fromthe coding sequence of SEQ ID NO:56 shown in FIG. 33.

[2616]FIG. 35 shows a nucleotide sequence (SEQ ID NO:61) of a nativesequence PRO1310 cDNA, wherein SEQ ID NO:61 is a clone designated hereinas “DNA47394-1572.

[2617]FIG. 36 shows the amino acid sequence (SEQ ID NO:62) derived fromthe coding sequence of SEQ ID NO:61 shown in FIG. 35.

[2618]FIG. 37 shows a nucleotide sequence (SEQ ID NO:66) of a nativesequence PRO698 (UNQ362) cDNA, wherein SEQ ID NO:66 is a clonedesignated herein as “DNA48320-1433”.

[2619]FIG. 38 shows the amino acid sequence (SEQ ID NO:67) derived fromthe coding sequence of SEQ ID NO:66 shown in FIG. 37.

[2620]FIG. 39 shows a nucleotide sequence designated herein as DNA39906(SEQ ID NO:68).

[2621]FIG. 40 shows a nucleotide sequence (SEQ ID NO:72) of a nativesequence PRO732 (UNQ396) cDNA, wherein SEQ ID NO:72 is a clonedesignated herein as “DNA48334-1435”.

[2622]FIG. 41 shows the amino acid sequence (SEQ ID NO:73) derived fromthe coding sequence of SEQ ID NO:72 shown in FIG. 40.

[2623]FIG. 42 shows a nucleotide sequence designated herein as DNA20239(SEQ ID NO:74).

[2624]FIG. 43 shows a nucleotide sequence designated herein as DNA38050(SEQ ID NO:75).

[2625]FIG. 44 shows a nucleotide sequence designated herein as DNA40683(SEQ ID NO:76).

[2626]FIG. 45 shows a nucleotide sequence designated herein as DNA42580(SEQ ID NO:77).

[2627]FIG. 46 shows a nucleotide sequence (SEQ ID NO:83) of a nativesequence PRO1120 (UNQ559) cDNA, wherein SEQ ID NO:83 is a clonedesignated herein as “DNA48606-1479”.

[2628]FIG. 47 shows the amino acid sequence (SEQ ID NO:84) derived fromthe coding sequence of SEQ ID NO:83 shown in FIG. 46.

[2629]FIG. 48 shows a nucleotide sequence (SEQ ID NO:94) of a nativesequence PRO537 (UNQ338) cDNA, wherein SEQ ID NO:94 is a clonedesignated herein as “DNA49141-1431”.

[2630]FIG. 49 shows the amino acid sequence (SEQ ID NO:95) derived fromthe coding sequence of SEQ ID NO:94 shown in FIG. 48.

[2631]FIG. 50 shows a nucleotide sequence (SEQ ID NO:96) of a nativesequence PRO536 (UNQ337) cDNA, wherein SEQ ID NO:96 is a clonedesignated herein as “DNA49142-1430”.

[2632]FIG. 51 shows the amino acid sequence (SEQ ID NO:97) derived fromthe coding sequence of SEQ ID NO:96 shown in FIG. 50.

[2633]FIG. 52 shows a nucleotide sequence (SEQ ID NO:98) of a nativesequence PRO535 (UNQ336) cDNA, wherein SEQ ID NO:98 is a clonedesignated herein as “DNA49143-1429”.

[2634]FIG. 53 shows the amino acid sequence (SEQ ID NO:99) derived fromthe coding sequence of SEQ ID NO:98 shown in FIG. 52.

[2635]FIG. 54 shows a nucleotide sequence designated herein as DNA30861(SEQ ID NO:100).

[2636]FIG. 55 shows a nucleotide sequence designated herein as DNA36351(SEQ ID NO:101).

[2637]FIG. 56 shows a nucleotide sequence (SEQ ID NO:102) of a nativesequence PRO718 (UNQ386) cDNA, wherein SEQ ID NO:102 is a clonedesignated herein as “DNA49647-1398”.

[2638]FIG. 57 shows the amino acid sequence (SEQ ID NO:103) derived fromthe coding sequence of SEQ ID NO:102 shown in FIG. 56.

[2639]FIG. 58 shows a nucleotide sequence designated herein as DNA15386(SEQ ID NO:104).

[2640]FIG. 59 shows a nucleotide sequence designated herein as DNA16630(SEQ ID NO:105).

[2641]FIG. 60 shows a nucleotide sequence designated herein as DNA16829(SEQ ID NO:106).

[2642]FIG. 61 shows a nucleotide sequence designated herein as DNA28357(SEQ ID NO:107).

[2643]FIG. 62 shows a nucleotide sequence designated herein as DNA43512(SEQ ID NO:108).

[2644]FIG. 63 shows a nucleotide sequence (SEQ ID NO:112) of a nativesequence PRO872 (UNQ439) cDNA, wherein SEQ ID NO:112 is a clonedesignated herein as “DNA49819-1439”.

[2645]FIG. 64 shows the amino acid sequence (SEQ ID NO:113) derived fromthe coding sequence of SEQ ID NO:112 shown in FIG. 63.

[2646]FIG. 65 shows a nucleotide sequence (SEQ ID NO:114) of a nativesequence PRO1063 (UNQ128) cDNA, wherein SEQ ID NO:114 is a clonedesignated herein as “DNA49820-1427”.

[2647]FIG. 66 shows the amino acid sequence (SEQ ID NO:115) derived fromthe coding sequence of SEQ ID NO:114 shown in FIG. 65.

[2648]FIG. 67 shows a nucleotide sequence (SEQ ID NO:116) of a nativesequence PRO619 (UNQ355) cDNA, wherein SEQ ID NO:116 is a clonedesignated herein as “DNA49821-1562”.

[2649]FIG. 68 shows the amino acid sequence (SEQ ID NO:117) derived fromthe coding sequence of SEQ ID NO:116 shown in FIG. 67.

[2650]FIG. 69 shows a nucleotide sequence (SEQ ID NO:118) of a nativesequence PRO943 (UNQ480) cDNA, wherein SEQ ID NO:118 is a clonedesignated herein as “DNA52192-1369”.

[2651]FIG. 70 shows the amino acid sequence (SEQ ID NO:119) derived fromthe coding sequence of SEQ ID NO:118 shown in FIG. 69.

[2652]FIG. 71 shows a nucleotide sequence (SEQ ID NO:123) of a nativesequence PRO1188 (UNQ602) cDNA, wherein SEQ ID NO:123 is a clonedesignated herein as “DNA52598-1518”.

[2653]FIG. 72 shows the amino acid sequence (SEQ ID NO:124) derived fromthe coding sequence of SEQ ID NO:123 shown in FIG. 71.

[2654]FIG. 73 shows a nucleotide sequence (SEQ ID NO:128) of a nativesequence PRO1133 (UNQ571) cDNA, wherein SEQ ID NO:128 is a clonedesignated herein as “DNA53913-1490”.

[2655]FIG. 74 shows the amino acid sequence (SEQ ID NO:129) derived fromthe coding sequence of SEQ ID NO:128 shown in FIG. 73.

[2656]FIG. 75 shows a nucleotide sequence (SEQ ID NO:134) of a nativesequence PRO784 (UNQ459) cDNA, wherein SEQ ID NO:134 is a clonedesignated herein as “DNA53978-1443”.

[2657]FIG. 76 shows the amino acid sequence (SEQ ID NO:135) derived fromthe coding sequence of SEQ ID NO:134 shown in FIG. 75.

[2658]FIG. 77 shows a nucleotide sequence designated herein as DNA44661(SEQ ID NO:136).

[2659]FIG. 78 shows a nucleotide sequence (SEQ ID NO:137) of a nativesequence PRO783 (UNQ458) cDNA, wherein SEQ ID NO:137 is a clonedesignated herein as “DNA53996-1442”.

[2660]FIG. 79 shows the amino acid sequence (SEQ ID NO:138) derived fromthe coding sequence of SEQ ID NO:137 shown in FIG. 78.

[2661]FIG. 80 shows a nucleotide sequence designated herein as DNA45201(SEQ ID NO:139).

[2662]FIG. 81 shows a nucleotide sequence designated herein as DNA14575(SEQ ID NO:140).

[2663]FIG. 82 shows a nucleotide sequence (SEQ ID NO:145) of a nativesequence PRO820 (UNQ503) cDNA, wherein SEQ ID NO:145 is a clonedesignated herein as “DNA56041-1416”.

[2664]FIG. 83 shows the amino acid sequence (SEQ ID NO:146) derived fromthe coding sequence of SEQ ID NO:145 shown in FIG. 82.

[2665]FIG. 84 shows a nucleotide sequence (SEQ ID NO:147) of a nativesequence PRO1080 (UNQ537) cDNA, wherein SEQ ID NO:147 is a clonedesignated herein as “DNA56047-1456”.

[2666]FIG. 85 shows the amino acid sequence (SEQ ID NO:148) derived fromthe coding sequence of SEQ ID NO:147 shown in FIG. 84.

[2667]FIG. 86 shows a nucleotide sequence designated herein as DNA36527(SEQ ID NO:149).

[2668]FIG. 87 shows a nucleotide sequence (SEQ ID NO:150) of a nativesequence PRO1079 (UNQ536) cDNA, wherein SEQ ID NO:150 is a clonedesignated herein as “DNA56050-1455”.

[2669]FIG. 88 shows the amino acid sequence (SEQ ID NO:151) derived fromthe coding sequence of SEQ ID NO:150 shown in FIG. 87.

[2670]FIG. 89 shows a nucleotide sequence (SEQ ID NO:152) of a nativesequence PRO793 (UNQ432) cDNA, wherein SEQ ID NO:152 is a clonedesignated herein as “DNA56110-1437”.

[2671]FIG. 90 shows the amino acid sequence (SEQ ID NO:153) derived fromthe coding sequence of SEQ ID NO:152 shown in FIG. 89.

[2672]FIG. 91 shows a nucleotide sequence designated herein as DNA50177(SEQ ID NO:154).

[2673]FIG. 92 shows a nucleotide sequence (SEQ ID NO:155) of a nativesequence PRO1016 (UNQ499) cDNA, wherein SEQ ID NO:155 is a clonedesignated herein as “DNA56113-1378”.

[2674]FIG. 93 shows the amino acid sequence (SEQ ID NO:156) derived fromthe coding sequence of SEQ ID NO:155 shown in FIG. 92.

[2675]FIG. 94 shows a nucleotide sequence (SEQ ID NO:157) of a nativesequence PRO1013 (UNQ496) cDNA, wherein SEQ ID NO:157 is a clonedesignated herein as “DNA56410-1414”.

[2676]FIG. 95 shows the amino acid sequence (SEQ ID NO:158) derived fromthe coding sequence of SEQ ID NO:157 shown in FIG. 94.

[2677]FIG. 96 shows a nucleotide sequence (SEQ ID NO:159) of a nativesequence PRO937 (UNQ474) cDNA, wherein SEQ ID NO:159 is a clonedesignated herein as “DNA56436-1448”.

[2678]FIG. 97 shows the amino acid sequence (SEQ ID NO:160) derived fromthe coding sequence of SEQ ID NO:159 shown in FIG. 96.

[2679]FIG. 98 shows a nucleotide sequence (SEQ ID NO:164) of a nativesequence PRO842 (UNQ473) cDNA, wherein SEQ ID NO:164 is a clonedesignated herein as “DNA56855-1447”.

[2680]FIG. 99 shows the amino acid sequence (SEQ ID NO:165) derived fromthe coding sequence of SEQ ID NO:164 shown in FIG. 98.

[2681]FIG. 100 shows a nucleotide sequence (SEQ ID NO:166) of a nativesequence PRO839 (UNQ472) cDNA, wherein SEQ ID NO:166 is a clonedesignated herein as “DNA56859-1445”.

[2682]FIG. 101 shows the amino acid sequence (SEQ ID NO:167) derivedfrom the coding sequence of SEQ ID NO:166 shown in FIG. 100.

[2683]FIG. 102 shows a nucleotide sequence (SEQ ID NO:168) of a nativesequence PRO1180 (UNQ594) cDNA, wherein SEQ ID NO:168 is a clonedesignated herein as “DNA56860-1510”.

[2684]FIG. 103 shows the amino acid sequence (SEQ ID NO:169) derivedfrom the coding sequence of SEQ ID NO:168 shown in FIG. 102.

[2685]FIG. 104 shows a nucleotide sequence (SEQ ID NO:170) of a nativesequence PRO1134 (UNQ572) cDNA, wherein SEQ ID NO:170 is a clonedesignated herein as “DNA56865-1491”.

[2686]FIG. 105 shows the amino acid sequence (SEQ ID NO:171) derivedfrom the coding sequence of SEQ ID NO:170 shown in FIG. 104.

[2687]FIG. 106 shows a nucleotide sequence designated herein as DNA52352(SEQ ID NO:172).

[2688]FIG. 107 shows a nucleotide sequence designated herein as DNA55725(SEQ ID NO:173).

[2689]FIG. 108 shows a nucleotide sequence (SEQ ID NO:174) of a nativesequence PRO830 (UNQ470) cDNA, wherein SEQ ID NO:174 is a clonedesignated herein as “DNA56866-1342”.

[2690]FIG. 109 shows the amino acid sequence (SEQ ID NO:175) derivedfrom the coding sequence of SEQ ID NO:174 shown in FIG. 108.

[2691]FIG. 110 shows a nucleotide sequence (SEQ ID NO:176) of a nativesequence PRO1115 (UNQ558) cDNA, wherein SEQ ID NO:176 is a clonedesignated herein as “DNA56868-1478”.

[2692]FIG. 111 shows the amino acid sequence (SEQ ID NO:177) derivedfrom the coding sequence of SEQ ID NO:176 shown in FIG. 110.

[2693]FIG. 112 shows a nucleotide sequence (SEQ ID NO:178) of a nativesequence PRO1277 (UNQ647) cDNA, wherein SEQ ID NO:178 is a clonedesignated herein as “DNA56869-1545”.

[2694]FIG. 113 shows the amino acid sequence (SEQ ID NO:179) derivedfrom the coding sequence of SEQ ID NO:178 shown in FIG. 112.

[2695]FIG. 114 shows a nucleotide sequence (SEQ ID NO:180) of a nativesequence PRO1135 (UNQ573) cDNA, wherein SEQ ID NO:180 is a clonedesignated herein as “DNA56870-1492”.

[2696]FIG. 115 shows the amino acid sequence (SEQ ID NO:181) derivedfrom the coding sequence of SEQ ID NO:180 shown in FIG. 114.

[2697]FIG. 116 shows a nucleotide sequence (SEQ ID NO:182) of a nativesequence PRO114 (UNQ557) cDNA, wherein SEQ ID NO:182 is a clonedesignated herein as “DNA57033-1403”.

[2698]FIG. 117 shows the amino acid sequence (SEQ ID NO:183) derivedfrom the coding sequence of SEQ ID NO:182 shown in FIG. 116.

[2699]FIG. 118 shows a nucleotide sequence designated herein as DNA48466(SEQ ID NO:184).

[2700]FIG. 119 shows a nucleotide sequence (SEQ ID NO:188) of a nativesequence PRO828 (UNQ469) cDNA, wherein SEQ ID NO:188 is a clonedesignated herein as “DNA57037-1444”.

[2701]FIG. 120 shows the amino acid sequence (SEQ ID NO:189) derivedfrom the coding sequence of SEQ ID NO:188 shown in FIG. 119.

[2702]FIG. 121 shows a nucleotide sequence (SEQ ID NO:193) of a nativesequence PRO1009 (UNQ493) cDNA, wherein SEQ ID NO:193 is a clonedesignated herein as “DNA57129-1413”.

[2703]FIG. 122 shows the amino acid sequence (SEQ ID NO:194) derivedfrom the coding sequence of SEQ ID NO:193 shown in FIG. 121.

[2704]FIG. 123 shows a nucleotide sequence designated herein as DNA50853(SEQ ID NO:195).

[2705]FIG. 124 shows a nucleotide sequence (SEQ ID NO:196) of a nativesequence PRO1007 (UNQ491) cDNA, wherein SEQ ID NO:196 is a clonedesignated herein as “DNA57690-1374”.

[2706]FIG. 125 shows the amino acid sequence (SEQ ID NO:197) derivedfrom the coding sequence of SEQ ID NO:196 shown in FIG. 124.

[2707]FIG. 126 shows a nucleotide sequence (SEQ ID NO:198) of a nativesequence PRO1056 (UNQ521) cDNA, wherein SEQ ID NO:198 is a clonedesignated herein as “DNA57693-1424”.

[2708]FIG. 127 shows the amino acid sequence (SEQ ID NO:199) derivedfrom the coding sequence of SEQ ID NO:198 shown in FIG. 126.

[2709]FIG. 128 shows a nucleotide sequence (SEQ ID NO:200) of a nativesequence PRO826 (UNQ467) cDNA, wherein SEQ ID NO:200 is a clonedesignated herein as “DNA57694-1341”.

[2710]FIG. 129 shows the amino acid sequence (SEQ ID NO:201) derivedfrom the coding sequence of SEQ ID NO:200 shown in FIG. 128.

[2711]FIG. 130 shows a nucleotide sequence (SEQ ID NO:202) of a nativesequence PRO819 (UNQ466) cDNA, wherein SEQ ID NO:202 is a clonedesignated herein as “DNA57695-1340”.

[2712]FIG. 131 shows the amino acid sequence (SEQ ID NO:203) derivedfrom the coding sequence of SEQ ID NO:202 shown in FIG. 130.

[2713]FIG. 132 shows a nucleotide sequence (SEQ ID NO:204) of a nativesequence PRO1006 (UNQ490) cDNA, wherein SEQ ID NO:204 is a clonedesignated herein as “DNA57699-1412”.

[2714]FIG. 133 shows the amino acid sequence (SEQ ID NO:205) derivedfrom the coding sequence of SEQ ID NO:204 shown in FIG. 132.

[2715]FIG. 134 shows a nucleotide sequence (SEQ ID NO:206) of a nativesequence PRO1112 (UNQ555) cDNA, wherein SEQ ID NO:206 is a clonedesignated herein as “DNA57702-1476”.

[2716]FIG. 135 shows the amino acid sequence (SEQ ID NO:207) derivedfrom the coding sequence of SEQ ID NO:206 shown in FIG. 134.

[2717]FIG. 136 shows a nucleotide sequence (SEQ ID NO:208) of a nativesequence PRO1074 (UNQ531) cDNA, wherein SEQ ID NO:208 is a clonedesignated herein as “DNA57704-1452”.

[2718]FIG. 137 shows the amino acid sequence (SEQ ID NO:209) derivedfrom the coding sequence of SEQ ID NO:208 shown in FIG. 136.

[2719]FIG. 138 shows a nucleotide sequence (SEQ ID NO:210) of a nativesequence PRO1005 (UNQ489) cDNA, wherein SEQ ID NO:210 is a clonedesignated herein as “DNA57708-1005”.

[2720]FIG. 139 shows the amino acid sequence (SEQ ID NO:211) derivedfrom the coding sequence of SEQ ID NO:210 shown in FIG. 138.

[2721]FIG. 140 shows a nucleotide sequence (SEQ ID NO:212) of a nativesequence PRO1073 (UNQ530) cDNA, wherein SEQ ID NO:212 is a clonedesignated herein as “DNA57710-1451”.

[2722]FIG. 141 shows the amino acid sequence (SEQ ID NO:213) derivedfrom the coding sequence of SEQ ID NO:212 shown in FIG. 140.

[2723]FIG. 142 shows a nucleotide sequence designated herein as DNA55938(SEQ ID NO:214).

[2724]FIG. 143 shows a nucleotide sequence (SEQ ID NO:215) of a nativesequence PRO1152 (UNQ582) cDNA, wherein SEQ ID NO:215 is a clonedesignated herein as “DNA57711-1501”.

[2725]FIG. 144 shows the amino acid sequence (SEQ ID NO:216) derivedfrom the coding sequence of SEQ ID NO:215 shown in FIG. 143.

[2726]FIG. 145 shows a nucleotide sequence designated herein as DNA55807(SEQ ID NO:217).

[2727]FIG. 146 shows a nucleotide sequence (SEQ ID NO:218) of a nativesequence PRO1136 (UNQ574) cDNA, wherein SEQ ID NO:218 is a clonedesignated herein as “DNA57827-1493”.

[2728]FIG. 147 shows the amino acid sequence (SEQ ID NO:219) derivedfrom the coding sequence of SEQ ID NO:218 shown in FIG. 146.

[2729]FIG. 148 shows a nucleotide sequence (SEQ ID NO:220) of a nativesequence PRO813 (UNQ465) cDNA, wherein SEQ ID NO:220 is a clonedesignated herein as “DNA57834-1339”.

[2730]FIG. 149 shows the amino acid sequence (SEQ ID NO:221) derivedfrom the coding sequence of SEQ ID NO:220 shown in FIG. 148.

[2731]FIG. 150 shows a nucleotide sequence (SEQ ID NO:222) of a nativesequence PRO809 (UNQ464) cDNA, wherein SEQ ID NO:222 is a clonedesignated herein as “DNA57836-1338”.

[2732]FIG. 151 shows the amino acid sequence (SEQ ID NO:223) derivedfrom the coding sequence of SEQ ID NO:222 shown in FIG. 150.

[2733]FIG. 152 shows a nucleotide sequence (SEQ ID NO:224) of a nativesequence PRO791 (UNQ463) cDNA, wherein SEQ ID NO:224 is a clonedesignated herein as “DNA57838-1337”.

[2734]FIG. 153 shows the amino acid sequence (SEQ ID NO:225) derivedfrom the coding sequence of SEQ ID NO:224 shown in FIG. 152.

[2735]FIG. 154 shows a nucleotide sequence (SEQ ID NO:226) of a nativesequence PRO1004 (UNQ488) cDNA, wherein SEQ ID NO:226 is a clonedesignated herein as “DNA57844-1410”.

[2736]FIG. 155 shows the amino acid sequence (SEQ ID NO:227) derivedfrom the coding sequence of SEQ ID NO:226 shown in FIG. 154.

[2737]FIG. 156 shows a nucleotide sequence (SEQ ID NO:228) of a nativesequence PRO1111 (UNQ554) cDNA, wherein SEQ ID NO:228 is a clonedesignated herein as “DNA58721-1475”.

[2738]FIG. 157 shows the amino acid sequence (SEQ ID NO:229) derivedfrom the coding sequence of SEQ ID NO:228 shown in FIG. 156.

[2739]FIG. 158 shows a nucleotide sequence (SEQ ID NO:230) of a nativesequence PRO1344 (UNQ699) cDNA, wherein SEQ ID NO:230 is a clonedesignated herein as “DNA58723-1588”.

[2740]FIG. 159 shows the amino acid sequence (SEQ ID NO:231) derivedfrom the coding sequence of SEQ ID NO:230 shown in FIG. 158.

[2741]FIG. 160 shows a nucleotide sequence (SEQ ID NO:235) of a nativesequence PRO1109 (UNQ552) cDNA, wherein SEQ ID NO:235 is a clonedesignated herein as “DNA58737-1473”.

[2742]FIG. 161 shows the amino acid sequence (SEQ ID NO:236) derivedfrom the coding sequence of SEQ ID NO:235 shown in FIG. 160.

[2743]FIG. 162 shows a nucleotide sequence (SEQ ID NO:240) of a nativesequence PRO1383 (UNQ719) cDNA, wherein SEQ ID NO:240 is a clonedesignated herein as “DNA58743-1609”.

[2744]FIG. 163 shows the amino acid sequence (SEQ ID NO:241) derivedfrom the coding sequence of SEQ ID NO:240 shown in FIG. 162.

[2745]FIG. 164 shows a nucleotide sequence (SEQ ID NO:245) of a nativesequence PRO1003 (UNQ487) cDNA, wherein SEQ ID NO:245 is a clonedesignated herein as “DNA58846-1409”.

[2746]FIG. 165 shows the amino acid sequence (SEQ ID NO:246) derivedfrom the coding sequence of SEQ ID NO:245 shown in FIG. 164.

[2747]FIG. 166 shows a nucleotide sequence (SEQ ID NO:247) of a nativesequence PRO1108 (UNQ551) cDNA, wherein SEQ ID NO:247 is a clonedesignated herein as “DNA58848-1472”.

[2748]FIG. 167 shows the amino acid sequence (SEQ ID NO:248) derivedfrom the coding sequence of SEQ ID NO:247 shown in FIG. 166.

[2749]FIG. 168 shows a nucleotide sequence (SEQ ID NO:249) of a nativesequence PRO1137 (UNQ575) cDNA, wherein SEQ ID NO:249 is a clonedesignated herein as “DNA58849-1494”.

[2750]FIG. 169 shows the amino acid sequence (SEQ ID NO:250) derivedfrom the coding sequence of SEQ ID NO:249 shown in FIG. 168.

[2751]FIG. 170 shows a nucleotide sequence (SEQ ID NO:252) of a nativesequence PRO1138 (UNQ576) cDNA, wherein SEQ ID NO:252 is a clonedesignated herein as “DNA58850-1495”.

[2752]FIG. 171 shows the amino acid sequence (SEQ ID NO:253) derivedfrom the coding sequence of SEQ ID NO:252 shown in FIG. 170.

[2753]FIG. 172 shows a nucleotide sequence designated herein as DNA49140(SEQ ID NO:254).

[2754]FIG. 173 shows a nucleotide sequence (SEQ ID NO:255) of a nativesequence PRO1054 (UNQ519) cDNA, wherein SEQ ID NO:255 is a clonedesignated herein as “DNA58853-1423”.

[2755]FIG. 174 shows the amino acid sequence (SEQ ID NO:256) derivedfrom the coding sequence of SEQ ID NO:255 shown in FIG. 173.

[2756]FIG. 175 shows a nucleotide sequence (SEQ ID NO:257) of a nativesequence PRO994 (UNQ518) cDNA, wherein SEQ ID NO:257 is a clonedesignated herein as “DNA58855-1422”.

[2757]FIG. 176 shows the amino acid sequence (SEQ ID NO:258) derivedfrom the coding sequence of SEQ ID NO:257 shown in FIG. 175.

[2758]FIG. 177 shows a nucleotide sequence (SEQ ID NO:259) of a nativesequence PRO812 (UNQ517) cDNA, wherein SEQ ID NO:259 is a clonedesignated herein as “DNA59205-1421”.

[2759]FIG. 178 shows the amino acid sequence (SEQ ID NO:260) derivedfrom the coding sequence of SEQ ID NO:259 shown in FIG. 177.

[2760]FIG. 179 shows a nucleotide sequence (SEQ ID NO:261) of a nativesequence PRO1069 (UNQ526) cDNA, wherein SEQ ID NO:261 is a clonedesignated herein as “DNA59211-1450”.

[2761]FIG. 180 shows the amino acid sequence (SEQ ID NO:262) derivedfrom the coding sequence of SEQ ID NO:261 shown in FIG. 179.

[2762]FIG. 181 shows a nucleotide sequence (SEQ ID NO:263) of a nativesequence PRO1129 (UNQ568) cDNA, wherein SEQ ID NO:263 is a clonedesignated herein as “DNA59213-1487”.

[2763]FIG. 182 shows the amino acid sequence (SEQ ID NO:264) derivedfrom the coding sequence of SEQ ID NO:263 shown in FIG. 181.

[2764]FIG. 183 shows a nucleotide sequence (SEQ ID NO:265) of a nativesequence PRO1068 (UNQ525) cDNA, wherein SEQ ID NO:265 is a clonedesignated herein as “DNA59214-1449”.

[2765]FIG. 184 shows the amino acid sequence (SEQ ID NO:266) derivedfrom the coding sequence of SEQ ID NO:265 shown in FIG. 183.

[2766]FIG. 185 shows a nucleotide sequence (SEQ ID NO:267) of a nativesequence PRO1066 (UNQ524) cDNA, wherein SEQ ID NO:267 is a clonedesignated herein as “DNA59215-1425”.

[2767]FIG. 186 shows the amino acid sequence (SEQ ID NO:268) derivedfrom the coding sequence of SEQ ID NO:267 shown in FIG. 185.

[2768]FIG. 187 shows a nucleotide sequence (SEQ ID NO:269) of a nativesequence PRO1184 (UNQ598) cDNA, wherein SEQ ID NO:269 is a clonedesignated herein as “DNA59220-1514”.

[2769]FIG. 188 shows the amino acid sequence (SEQ ID NO:270) derivedfrom the coding sequence of SEQ ID NO:269 shown in FIG. 187.

[2770]FIG. 189 shows a nucleotide sequence (SEQ ID NO:271) of a nativesequence PRO1360 (UNQ709) cDNA, wherein SEQ ID NO:271 is a clonedesignated herein as “DNA59488-1603”.

[2771]FIG. 190 shows the amino acid sequence (SEQ ID NO:272) derivedfrom the coding sequence of SEQ ID NO:271 shown in FIG. 189.

[2772]FIG. 191 shows a nucleotide sequence (SEQ ID NO:273) of a nativesequence PRO1029 (UNQ514) cDNA, wherein SEQ ID NO:273 is a clonedesignated herein as “DNA59493-1420”.

[2773]FIG. 192 shows the amino acid sequence (SEQ ID NO:274) derivedfrom the coding sequence of SEQ ID NO:273 shown in FIG. 191.

[2774]FIG. 193 shows a nucleotide sequence (SEQ ID NO:275) of a nativesequence PRO1139 (UNQ577) cDNA, wherein SEQ ID NO:275 is a clonedesignated herein as “DNA59497-1496”.

[2775]FIG. 194 shows the amino acid sequence (SEQ ID NO:276) derivedfrom the coding sequence of SEQ ID NO:275 shown in FIG. 193.

[2776]FIG. 195 shows a nucleotide sequence (SEQ ID NO:277) of a nativesequence PRO1309 (UNQ675) cDNA, wherein SEQ ID NO:277 is a clonedesignated herein as “DNA59588-1571”.

[2777]FIG. 196 shows the amino acid sequence (SEQ ID NO:278) derivedfrom the coding sequence of SEQ ID NO:277 shown in FIG. 195.

[2778]FIG. 197 shows a nucleotide sequence (SEQ ID NO:280) of a nativesequence PRO1028 (UNQ513) cDNA, wherein SEQ ID NO:280 is a clonedesignated herein as “DNA59603-1419”.

[2779]FIG. 198 shows the amino acid sequence (SEQ ID NO:281) derivedfrom the coding sequence of SEQ ID NO:280 shown in FIG. 197.

[2780]FIG. 199 shows a nucleotide sequence (SEQ ID NO:282) of a nativesequence PRO1027 (UNQ512) cDNA, wherein SEQ ID NO:282 is a clonedesignated herein as “DNA59605-1418”.

[2781]FIG. 200 shows the amino acid sequence (SEQ ID NO:283) derivedfrom the coding sequence of SEQ ID NO:282 shown in FIG. 199.

[2782]FIG. 201 shows a nucleotide sequence (SEQ ID NO:284) of a nativesequence PRO1107 (UNQ550) cDNA, wherein SEQ ID NO:284 is a clonedesignated herein as “DNA59606-1471”.

[2783]FIG. 202 shows the amino acid sequence (SEQ ID NO:285) derivedfrom the coding sequence of SEQ ID NO:284 shown in FIG. 201.

[2784]FIG. 203 shows a nucleotide sequence (SEQ ID NO:286) of a nativesequence PRO1140 (UNQ578) cDNA, wherein SEQ ID NO:286 is a clonedesignated herein as “DNA59607-1497”.

[2785]FIG. 204 shows the amino acid sequence (SEQ ID NO:287) derivedfrom the coding sequence of SEQ ID NO:286 shown in FIG. 203.

[2786]FIG. 205 shows a nucleotide sequence (SEQ ID NO:288) of a nativesequence PRO1106 (UNQ549) cDNA, wherein SEQ ID NO:288 is a clonedesignated herein as “DNA59609-1470”.

[2787]FIG. 206 shows the amino acid sequence (SEQ ID NO:289) derivedfrom the coding sequence of SEQ ID NO:288 shown in FIG. 205.

[2788]FIG. 207 shows a nucleotide sequence (SEQ ID NO:290) of a nativesequence PRO1291 (UNQ659) cDNA, wherein SEQ ID NO:290 is a clonedesignated herein as “DNA59610-1556”.

[2789]FIG. 208 shows the amino acid sequence (SEQ ID NO:291) derivedfrom the coding sequence of SEQ ID NO:290 shown in FIG. 207.

[2790]FIG. 209 shows a nucleotide sequence (SEQ ID NO:292) of a nativesequence PRO1105 (UNQ548) cDNA, wherein SEQ ID NO:292 is a clonedesignated herein as “DNA59612-1466”.

[2791]FIG. 210 shows the amino acid sequence (SEQ ID NO:293) derivedfrom the coding sequence of SEQ ID NO:292 shown in FIG. 209.

[2792]FIG. 211 shows a nucleotide sequence (SEQ ID NO:294) of a nativesequence PRO511 (UNQ511) cDNA, wherein SEQ ID NO:294 is a clonedesignated herein as “DNA59613-1417”.

[2793]FIG. 212 shows the amino acid sequence (SEQ ID NO:295) derivedfrom the coding sequence of SEQ ID NO:294 shown in FIG. 211.

[2794]FIG. 213 shows a nucleotide sequence (SEQ ID NO:296) of a nativesequence PRO1104 (UNQ547) cDNA, wherein SEQ ID NO:296 is a clonedesignated herein as “DNA59616-1465”.

[2795]FIG. 214 shows the amino acid sequence (SEQ ID NO:297) derivedfrom the coding sequence of SEQ ID NO:296 shown in FIG. 213.

[2796]FIG. 215 shows a nucleotide sequence (SEQ ID NO:298) of a nativesequence PRO1100 (UNQ546) cDNA, wherein SEQ ID NO:298 is a clonedesignated herein as “DNA59619-1464”.

[2797]FIG. 216 shows the amino acid sequence (SEQ ID NO:299) derivedfrom the coding sequence of SEQ ID NO:298 shown in FIG. 215.

[2798]FIG. 217 shows a nucleotide sequence (SEQ ID NO:300) of a nativesequence PRO836 (UNQ545) cDNA, wherein SEQ ID NO:300 is a clonedesignated herein as “DNA59620-1463”.

[2799]FIG. 218 shows the amino acid sequence (SEQ ID NO:301) derivedfrom the coding sequence of SEQ ID NO:300 shown in FIG. 217.

[2800]FIG. 219 shows a nucleotide sequence (SEQ ID NO:302) of a nativesequence PRO1141 (UNQ579) cDNA, wherein SEQ ID NO:302 is a clonedesignated herein as “DNA59625-1498”.

[2801]FIG. 220 shows the amino acid sequence (SEQ ID NO:303) derivedfrom the coding sequence of SEQ ID NO:302 shown in FIG. 219.

[2802]FIG. 221 shows a nucleotide sequence designated herein as DNA33128(SEQ ID NO:304).

[2803]FIG. 222 shows a nucleotide sequence designated herein as DNA34256(SEQ ID NO:305).

[2804]FIG. 223 shows a nucleotide sequence designated herein as DNA47941(SEQ ID NO:306).

[2805]FIG. 224 shows a nucleotide sequence designated herein as DNA54389(SEQ ID NO:307).

[2806]FIG. 225 shows a nucleotide sequence (SEQ ID NO:308) of a nativesequence PRO1132 (UNQ570) cDNA, wherein SEQ ID NO:308 is a clonedesignated herein as “DNA59767-1489”.

[2807]FIG. 226 shows the amino acid sequence (SEQ ID NO:309) derivedfrom the coding sequence of SEQ ID NO:308 shown in FIG. 225.

[2808]FIG. 227 shows a nucleotide sequence (SEQ ID NO:313) of a nativesequence PRO1346 cDNA, wherein SEQ ID NO:313 is a clone designatedherein as “DNA59776-1600”.

[2809]FIG. 228 shows the amino acid sequence (SEQ ID NO:314) derivedfrom the coding sequence of SEQ ID NO:313 shown in FIG. 227.

[2810]FIG. 229 shows a nucleotide sequence (SEQ ID NO:318) of a nativesequence PRO1131 (UNQ569) cDNA, wherein SEQ ID NO:318 is a clonedesignated herein as “DNA59777-1480”.

[2811]FIG. 230 shows the amino acid sequence (SEQ ID NO:319) derivedfrom the coding sequence of SEQ ID NO:318 shown in FIG. 229.

[2812]FIG. 231 shows a nucleotide sequence designated herein as DNA43546(SEQ ID NO:320).

[2813]FIG. 232 shows a nucleotide sequence (SEQ ID NO:325) of a nativesequence PRO1281 (UNQ651) cDNA, wherein SEQ ID NO:325 is a clonedesignated herein as “DNA59820-1549”.

[2814]FIG. 233 shows the amino acid sequence (SEQ ID NO:326) derivedfrom the coding sequence of SEQ ID NO:325 shown in FIG. 232.

[2815]FIG. 234 shows a nucleotide sequence (SEQ ID NO:333) of a nativesequence PRO1064 (UNQ111) cDNA, wherein SEQ ID NO:333 is a clonedesignated herein as “DNA59827-1426”.

[2816]FIG. 235 shows the amino acid sequence (SEQ ID NO:334) derivedfrom the coding sequence of SEQ ID NO:333 shown in FIG. 234.

[2817]FIG. 236 shows a nucleotide sequence designated herein as DNA45288(SEQ ID NO:335).

[2818]FIG. 237 shows a nucleotide sequence (SEQ ID NO:339) of a nativesequence PRO1379 (UNQ716) cDNA, wherein SEQ ID NO:339 is a clonedesignated herein as “DNA59828-1608”.

[2819]FIG. 238 shows the amino acid sequence (SEQ ID NO:340) derivedfrom the coding sequence of SEQ ID NO:339 shown in FIG. 237.

[2820]FIG. 239 shows a nucleotide sequence (SEQ ID NO:344) of a nativesequence PRO844 (UNQ544) cDNA, wherein SEQ ID NO:344 is a clonedesignated herein as “DNA59838-1462”.

[2821]FIG. 240 shows the amino acid sequence (SEQ ID NO:345) derivedfrom the coding sequence of SEQ ID NO:344 shown in FIG. 239.

[2822]FIG. 241 shows a nucleotide sequence (SEQ ID NO:346) of a nativesequence PRO848 (UNQ543) cDNA, wherein SEQ ID NO:346 is a clonedesignated herein as “DNA59839-1461”.

[2823]FIG. 242 shows the amino acid sequence (SEQ ID NO:347) derivedfrom the coding sequence of SEQ ID NO:346 shown in FIG. 241.

[2824]FIG. 243 shows a nucleotide sequence (SEQ ID NO:348) of a nativesequence PRO1097 (UNQ542) cDNA, wherein SEQ ID NO:348 is a clonedesignated herein as “DNA59841-1460”.

[2825]FIG. 244 shows the amino acid sequence (SEQ ID NO:349) derivedfrom the coding sequence of SEQ ID NO:348 shown in FIG. 243.

[2826]FIG. 245 shows a nucleotide sequence (SEQ ID NO:350) of a nativesequence PRO1153 (UNQ583) cDNA, wherein SEQ ID NO:350 is a clonedesignated herein as “DNA59842-1502”.

[2827]FIG. 246 shows the amino acid sequence (SEQ ID NO:351) derivedfrom the coding sequence of SEQ ID NO:350 shown in FIG. 245.

[2828]FIG. 247 shows a nucleotide sequence (SEQ ID NO:352) of a nativesequence PRO1154 (UNQ584) cDNA, wherein SEQ ID NO:352 is a clonedesignated herein as “DNA59846-1503”.

[2829]FIG. 248 shows the amino acid sequence (SEQ ID NO:353) derivedfrom the coding sequence of SEQ ID NO:352 shown in FIG. 247.

[2830]FIG. 249 shows a nucleotide sequence (SEQ ID NO:354) of a nativesequence PRO1181 (UNQ595) cDNA, wherein SEQ ID NO:354 is a clonedesignated herein as “DNA59847-1511”.

[2831]FIG. 250 shows the amino acid sequence (SEQ ID NO:355) derivedfrom the coding sequence of SEQ ID NO:354 shown in FIG. 249.

[2832]FIG. 251 shows a nucleotide sequence (SEQ ID NO:356) of a nativesequence PRO1182 (UNQ596) cDNA, wherein SEQ ID NO:356 is a clonedesignated herein as “DNA59848-1512”.

[2833]FIG. 252 shows the amino acid sequence (SEQ ID NO:357) derivedfrom the coding sequence of SEQ ID NO:356 shown in FIG. 251.

[2834]FIG. 253 shows a nucleotide sequence (SEQ ID NO:358) of a nativesequence PRO1155 (UNQ585) cDNA, wherein SEQ ID NO:358 is a clonedesignated herein as “DNA59849-1504”.

[2835]FIG. 254 shows the amino acid sequence (SEQ ID NO:359) derivedfrom the coding sequence of SEQ ID NO:358 shown in FIG. 253.

[2836]FIG. 255 shows a nucleotide sequence (SEQ ID NO:360) of a nativesequence PRO1156 (UNQ586) cDNA, wherein SEQ ID NO:360 is a clonedesignated herein as “DNA59853-1505”.

[2837]FIG. 256 shows the amino acid sequence (SEQ ID NO:361) derivedfrom the coding sequence of SEQ ID NO:360 shown in FIG. 255.

[2838]FIG. 257 shows a nucleotide sequence (SEQ ID NO:362) of a nativesequence PRO1098 (UNQ541) cDNA, wherein SEQ ID NO:362 is a clonedesignated herein as “DNA59854-1459”.

[2839]FIG. 258 shows the amino acid sequence (SEQ ID NO:363) derivedfrom the coding sequence of SEQ ID NO:362 shown in FIG. 257.

[2840]FIG. 259 shows a nucleotide sequence (SEQ ID NO:364) of a nativesequence PRO1127 (UNQ565) cDNA, wherein SEQ ID NO:364 is a clonedesignated herein as “DNA60283-1484”.

[2841]FIG. 260 shows the amino acid sequence (SEQ ID NO:365) derivedfrom the coding sequence of SEQ ID NO:364 shown in FIG. 259.

[2842]FIG. 261 shows a nucleotide sequence (SEQ ID NO:366) of a nativesequence PRO1126 (UNQ564) cDNA, wherein SEQ ID NO:366 is a clonedesignated herein as “DNA60615-1483”.

[2843]FIG. 262 shows the amino acid sequence (SEQ ID NO:367) derivedfrom the coding sequence of SEQ ID NO:366 shown in FIG. 261.

[2844]FIG. 263 shows a nucleotide sequence (SEQ ID NO:368) of a nativesequence PRO1125 (UNQ563) cDNA, wherein SEQ ID NO:368 is a clonedesignated herein as “DNA60619-1482”.

[2845]FIG. 264 shows the amino acid sequence (SEQ ID NO:369) derivedfrom the coding sequence of SEQ ID NO:368 shown in FIG. 263.

[2846]FIG. 265 shows a nucleotide sequence (SEQ ID NO:370) of a nativesequence PRO1186 (UNQ600) cDNA, wherein SEQ ID NO:370 is a clonedesignated herein as “DNA60621-1516”.

[2847]FIG. 266 shows the amino acid sequence (SEQ ID NO:371) derivedfrom the coding sequence of SEQ ID NO:370 shown in FIG. 265.

[2848]FIG. 267 shows a nucleotide sequence (SEQ ID NO:372) of a nativesequence PRO1198 (UNQ611) cDNA, wherein SEQ ID NO:372 is a clonedesignated herein as “DNA60622-1525 ”.

[2849]FIG. 268 shows the amino acid sequence (SEQ ID NO:373) derivedfrom the coding sequence of SEQ ID NO:372 shown in FIG. 267.

[2850]FIG. 269 shows a nucleotide sequence (SEQ ID NO:374) of a nativesequence PRO1158 (UNQ588) cDNA, wherein SEQ ID NO:374 is a clonedesignated herein as “DNA60625-1507”.

[2851]FIG. 270 shows the amino acid sequence (SEQ ID NO:375) derivedfrom the coding sequence of SEQ ID NO:374 shown in FIG. 269.

[2852]FIG. 271 shows a nucleotide sequence (SEQ ID NO:376) of a nativesequence PRO1159 (UNQ589) cDNA, wherein SEQ ID NO:376 is a clonedesignated herein as “DNA60627-1508”.

[2853]FIG. 272 shows the amino acid sequence (SEQ ID NO:377) derivedfrom the coding sequence of SEQ ID NO:376 shown in FIG. 271.

[2854]FIG. 273 shows a nucleotide sequence (SEQ ID NO:378) of a nativesequence PRO1124 (UNQ562) cDNA, wherein SEQ ID NO:378 is a clonedesignated herein as “DNA60629-1481”.

[2855]FIG. 274 shows the amino acid sequence (SEQ ID NO:379) derivedfrom the coding sequence of SEQ ID NO:378 shown in FIG. 273.

[2856]FIG. 275 shows a nucleotide sequence (SEQ ID NO:380) of a nativesequence PRO1287 (UNQ656) cDNA, wherein SEQ ID NO:380 is a clonedesignated herein as “DNA61755-1554”.

[2857]FIG. 276 shows the amino acid sequence (SEQ ID NO:381) derivedfrom the coding sequence of SEQ ID NO:380 shown in FIG. 275.

[2858]FIG. 277 shows a nucleotide sequence (SEQ ID NO:386) of a nativesequence PRO1312 (UNQ678) cDNA, wherein SEQ ID NO:386 is a clonedesignated herein as “DNA61873-1574”.

[2859]FIG. 278 shows the amino acid sequence (SEQ ID NO:387) derivedfrom the coding sequence of SEQ ID NO:386 shown in FIG. 277.

[2860]FIG. 279 shows a nucleotide sequence (SEQ ID NO:388) of a nativesequence PRO1192 (UNQ606) cDNA, wherein SEQ ID NO:388 is a clonedesignated herein as “DNA62814-1521”.

[2861]FIG. 280 shows the amino acid sequence (SEQ ID NO:389) derivedfrom the coding sequence of SEQ ID NO:388 shown in FIG. 279.

[2862]FIG. 281 shows a nucleotide sequence (SEQ ID NO:393) of a nativesequence PRO1160 (UNQ590) cDNA, wherein SEQ ID NO:393 is a clonedesignated herein as “DNA62872-1509”.

[2863]FIG. 282 shows the amino acid sequence (SEQ ID NO:394) derivedfrom the coding sequence of SEQ ID NO:393 shown in FIG. 281.

[2864]FIG. 283 shows a nucleotide sequence (SEQ ID NO:398) of a nativesequence PRO1187 (UNQ601) cDNA, wherein SEQ ID NO:398 is a clonedesignated herein as “DNA62876-1517”.

[2865]FIG. 284 shows the amino acid sequence (SEQ ID NO:399) derivedfrom the coding sequence of SEQ ID NO:398 shown in FIG. 283.

[2866]FIG. 285 shows a nucleotide sequence (SEQ ID NO:400) of a nativesequence PRO1185 (UNQ599) cDNA, wherein SEQ ID NO:400 is a clonedesignated herein as “DNA62881-1515”.

[2867]FIG. 286 shows the amino acid sequence (SEQ ID NO:401) derivedfrom the coding sequence of SEQ ID NO:400 shown in FIG. 285.

[2868]FIG. 287 shows a nucleotide sequence (SEQ ID NO:402) of a nativesequence PRO1345 (UNQ700) cDNA, wherein SEQ ID NO:402 is a clonedesignated herein as “DNA64852-1589”.

[2869]FIG. 288 shows the amino acid sequence (SEQ ID NO:403) derivedfrom the coding sequence of SEQ ID NO:402 shown in FIG. 287.

[2870]FIG. 289 shows a nucleotide sequence (SEQ ID NO:407) of a nativesequence PRO1245 (UNQ629) cDNA, wherein SEQ ID NO:407 is a clonedesignated herein as “DNA64884-1527”.

[2871]FIG. 290 shows the amino acid sequence (SEQ ID NO:408) derivedfrom the coding sequence of SEQ ID NO:407 shown in FIG. 289.

[2872]FIG. 291 shows a nucleotide sequence (SEQ ID NO:409) of a nativesequence PRO1358 (UNQ707) cDNA, wherein SEQ ID NO:409 is a clonedesignated herein as “DNA64890-1612”.

[2873]FIG. 292 shows the amino acid sequence (SEQ ID NO:410) derivedfrom the coding sequence of SEQ ID NO:409 shown in FIG. 291.

[2874]FIG. 293 shows a nucleotide sequence (SEQ ID NO:411) of a nativesequence PRO1195 (UNQ608) cDNA, wherein SEQ ID NO:411 is a clonedesignated herein as “DNA65412-1523”.

[2875]FIG. 294 shows the amino acid sequence (SEQ ID NO:412) derivedfrom the coding sequence of SEQ ID 140:411 shown in FIG. 293.

[2876]FIG. 295 shows a nucleotide sequence (SEQ ID NO:413) of a nativesequence PRO1270 (UNQ640) cDNA, wherein SEQ ID NO:413 is a clonedesignated herein as “DNA66308-1537”.

[2877]FIG. 296 shows the amino acid sequence (SEQ ID NO:414) derivedfrom the coding sequence of SEQ ID NO:413 shown in FIG. 295.

[2878]FIG. 297 shows a nucleotide sequence (SEQ ID NO:415) of a nativesequence PRO1271 (UNQ641) cDNA, wherein SEQ ID NO:415 is a clonedesignated herein as “DNA66309-1538”.

[2879]FIG. 298 shows the amino acid sequence (SEQ ID NO:416) derivedfrom the coding sequence of SEQ ID NO:415 shown in FIG. 297.

[2880]FIG. 299 shows a nucleotide sequence (SEQ ID NO:417) of a nativesequence PRO1375 (UNQ712) cDNA, wherein SEQ ID NO:417 is a clonedesignated herein as “DNA67004-1614”.

[2881]FIG. 300 shows the amino acid sequence (SEQ ID NO:418) derivedfrom the coding sequence of SEQ ID NO:417 shown in FIG. 299.

[2882]FIG. 301 shows a nucleotide sequence (SEQ ID NO:419) of a nativesequence PRO1385 (UNQ720) cDNA, wherein SEQ ID NO:419 is a clonedesignated herein as “DNA68869-1610”.

[2883]FIG. 302 shows the amino acid sequence (SEQ ID NO:420) derivedfrom the coding sequence of SEQ ID NO:419 shown in FIG. 301.

[2884]FIG. 303 shows a nucleotide sequence (SEQ ID NO:421) of a nativesequence PRO1387 (UNQ722) cDNA, wherein SEQ ID NO:421 is a clonedesignated herein as “DNA68872-1620”.

[2885]FIG. 304 shows the amino acid sequence (SEQ ID NO:422) derivedfrom the coding sequence of SEQ ID NO:421 shown in FIG. 303.

[2886]FIG. 305 shows a nucleotide sequence (SEQ ID NO:423) of a nativesequence PRO1384 (UNQ721) cDNA, wherein SEQ ID NO:423 is a clonedesignated herein as “DNA71159-1617”.

[2887]FIG. 306 shows the amino acid sequence (SEQ ID NO:424) derivedfrom the coding sequence of SEQ ID NO:423 shown in FIG. 305.

[2888]FIG. 307 shows a nucleotide sequence (SEQ ID NO:494) of a nativesequence PRO183 cDNA, wherein SEQ ID NO:494 is a clone designated hereinas “DNA28498”.

[2889]FIG. 308 shows the amino acid sequence (SEQ ID NO:495) derivedfrom the coding sequence of SEQ ID NO:494 shown in FIG. 307.

[2890]FIG. 309 shows a nucleotide sequence (SEQ ID NO:496) of a nativesequence PRO184 cDNA, wherein SEQ ID NO:496 is a clone designated hereinas “DNA28500.”

[2891]FIG. 310 shows the amino acid sequence (SEQ ID NO:497) derivedfrom the coding sequence of SEQ ID NO:496 shown in FIG. 309.

[2892]FIG. 311 shows a nucleotide sequence (SEQ ID NO:498) of a nativesequence PRO185 cDNA, wherein SEQ ID NO:498 is a clone designated hereinas “DNA28503”.

[2893]FIG. 312 shows the amino acid sequence (SEQ ID NO:499) derivedfrom the coding sequence of SEQ ID NO:498 shown in FIG. 311.

[2894]FIG. 313 shows a nucleotide sequence (SEQ ID NO:500) of a nativesequence PRO331 cDNA, wherein SEQ ID NO:500 is a clone designated hereinas “DNA40981-1234”.

[2895]FIG. 314 shows the amino acid sequence (SEQ ID NO:501) derivedfrom the coding sequence of SEQ ID NO:500 shown in FIG. 313.

[2896]FIG. 315 shows a nucleotide sequence (SEQ ID NO:502) of a nativesequence PRO363 cDNA, wherein SEQ ID NO:502 is a clone designated hereinas “DNA45419-1252”.

[2897]FIG. 316 shows the amino acid sequence (SEQ ID NO:503) derivedfrom the coding sequence of SEQ ID NO:502 shown in FIG. 315.

[2898]FIG. 317 shows a nucleotide sequence (SEQ ID NO:504) of a nativesequence PRO5723 cDNA, wherein SEQ ID NO:504 is a clone designatedherein as “DNA82361”.

[2899]FIG. 318 shows the amino acid sequence (SEQ ID NO:505) derivedfrom the coding sequence of SEQ ID NO:504 shown in FIG. 317.

[2900]FIG. 319 shows a nucleotide sequence (SEQ ID NO:506) of a nativesequence PRO3301 cDNA, wherein SEQ ID NO:506 is a clone designatedherein as “DNA88002”.

[2901]FIG. 320 shows the amino acid sequence (SEQ ID NO:507) derivedfrom the coding sequence of SEQ ID NO:506 shown in FIG. 319.

[2902]FIG. 321 shows a nucleotide sequence (SEQ ID NO:508) of a nativesequence PRO9940 cDNA, wherein SEQ ID NO:508 is a clone designatedherein as “DNA92282”.

[2903]FIG. 322 shows the amino acid sequence (SEQ ID NO:509) derivedfrom the coding sequence of SEQ ID NO:508 shown in FIG. 321.

[2904]FIG. 323 shows a nucleotide sequence (SEQ ID NO:510) of a nativesequence PRO9828 cDNA, wherein SEQ ID NO:510 is a clone designatedherein as “DNA142238-2768”.

[2905]FIG. 324 shows the amino acid sequence (SEQ ID NO:511) derivedfrom the coding sequence of SEQ ID NO:510 shown in FIG. 323.

[2906]FIG. 325 shows a nucleotide sequence (SEQ ID NO:512) of a nativesequence PRO7170 cDNA, wherein SEQ ID NO:512 is a clone designatedherein as “DNA108722-2743”.

[2907]FIG. 326 shows the amino acid sequence (SEQ ID NO:513) derivedfrom the coding sequence of SEQ ID NO:512 shown in FIG. 325.

[2908]FIG. 327 shows a nucleotide sequence (SEQ ID NO:514) of a nativesequence PRO361 cDNA, wherein SEQ ID NO:514 is a clone designated hereinas “DNA45410-1250”.

[2909]FIG. 328 shows the amino acid sequence (SEQ ID NO:515) derivedfrom the coding sequence of SEQ ID NO:514 shown in FIG. 327.

[2910]FIG. 329 shows a nucleotide sequence (SEQ ID NO:516) of a nativesequence PRO846 cDNA, wherein SEQ ID NO:516 is a clone designated hereinas “DNA44196-1353”.

[2911]FIG. 330 shows the amino acid sequence (SEQ ID NO:517) derivedfrom the coding sequence of SEQ ID NO:516 shown in FIG. 329.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[2912] I. Definitions

[2913] The terms “PRO polypeptide” and “PRO” as used herein and whenimmediately followed by a numerical designation refer to variouspolypeptides, wherein the complete designation (i.e., PRO/number) refersto specific polypeptide sequences as described herein. The terms“PRO/number polypeptide” and “PRO/number” wherein the term “nunber” isprovided as an actual numerical designation as used herein encompassnative sequence polypeptides and polypeptide variants (which are furtherdefined herein). The PRO polypeptides described herein may be isolatedfrom a variety of sources, such as from human tissue types or fromanother source, or prepared by recombinant or synthetic methods.

[2914] A “native sequence PRO polypeptide” comprises a polypeptidehaving the same amino acid sequence as the corresponding PRO polypeptidederived from nature. Such native sequence PRO polypeptides can beisolated from nature or can be produced by recombinant or syntheticmeans. The term “native sequence PRO polypeptide” specificallyencompasses naturally-occurring truncated or secreted forms of thespecific PRO polypeptide (e.g., an extracellular domain sequence),naturally-occurring variant forms (e.g., alternatively spliced forms)and naturally-occurring allelic variants of the polypeptide. In variousembodiments of the invention, the native sequence PRO polypeptidesdisclosed herein are mature or full-length native sequence polypeptidescomprising the full-length amino acids sequences shown in theaccompanying figures. Start and stop codons are shown in bold font andunderlined in the figures. However, while the PRO polypeptide disclosedin the accompanying figures are shown to begin with methionine residuesdesignated herein as amino acid position 1 in the figures, it isconceivable and possible that other methionine residues located eitherupstream or downstream from the amino acid position 1 in the figures maybe employed as the starting amino acid residue for the PRO polypeptides.

[2915] The PRO polypeptide “extracellular domain” or “ECD” refers to aform of the PRO polypeptide which is essentially free of thetransmembrane and cytoplasmic domains. Ordinarily, a PRO polypeptide ECDwill have less than 1% of such transmembrane and/or cytoplasmic domainsand preferably, will have less than 0.5% of such domains. It will beunderstood that any transmembrane domains identified for the PROpolypeptides of the present invention are identified pursuant tocriteria routinely employed in the art for identifying that type ofhydrophobic domain. The exact boundaries of a transmembrane domain mayvary but most likely by no more than about 5 amino acids at either endof the domain as initially identified herein. Optionally, therefore, anextracellular domain of a PRO polypeptide may contain from about 5 orfewer amino acids on either side of the transmembranedomain/extracellular domain boundary as identified in the Examples orspecification and such polypeptides, with or without the associatedsignal peptide, and nucleic acid encoding them, are comtemplated by thepresent invention.

[2916] The approximate location of the “signal peptides” of the variousPRO polypeptides disclosed herein are shown in the present specificationand/or the accompanying figures. It is noted, however, that theC-terminal boundary of a signal peptide may vary, but most likely by nomore than about 5 amino acids on either side of the signal peptideC-terminal boundary as initially identified herein, wherein theC-terminal boundary of the signal peptide may be identified pursuant tocriteria routinely employed in the art for identifying that type ofamino acid sequence element (e.g., Nielsen et al., Prot. Eng. 10:1-6(1997) and von Heinje et al., Nucl. Acids. Res. 14:4683-4690 (1986)).Moreover, it is also recognized that, in some cases, cleavage of asignal sequence from a secreted polypeptide is not entirely uniform,resulting in more than one secreted species. These mature polypeptides,where the signal peptide is cleaved within no more than about 5 aminoacids on either side of the C-terminal boundary of the signal peptide asidentified herein, and the polynucleotides encoding them, arecontemplated by the present invention.

[2917] “PRO polypeptide variant” means an active PRO polypeptide asdefined above or below having at least about 80% amino acid sequenceidentity with a full-length native sequence PRO polypeptide sequence asdisclosed herein, a PRO polypeptide sequence lacking the signal peptideas disclosed herein, an extracellular domain of a PRO polypeptide, withor without the signal peptide, as disclosed herein or any other fragmentof a full-length PRO polypeptide sequence as disclosed herein. Such PROpolypeptide variants include, for instance, PRO polypeptides wherein oneor more amino acid residues are added, or deleted, at the N- orC-terminus of the full-length native amino acid sequence. Ordinarily, aPRO polypeptide variant will have at least about 80% amino acid sequenceidentity, preferably at least about 81% amino acid sequence identity,more preferably at least about 82% amino acid sequence identity, morepreferably at least about 83% amino acid sequence identity, morepreferably at least about 84% amino acid sequence identity, morepreferably at least about 85% amino acid sequence identity, morepreferably at least about 86% amino acid sequence identity, morepreferably at least about 87% amino acid sequence identity, morepreferably at least about 88% amino acid sequence identity, morepreferably at least about 89% amino acid sequence identity, morepreferably at least about 90% amino acid sequence identity, morepreferably at least about 91% amino acid sequence identity, morepreferably at least about 92% amino acid sequence identity, morepreferably at least about 93% amino acid sequence identity, morepreferably at least about 94% amino acid sequence identity, morepreferably at least about 95% amino acid sequence identity, morepreferably at least about 96% amino acid sequence identity, morepreferably at least about 97% amino acid sequence identity, morepreferably at least about 98% amino acid sequence identity and mostpreferably at least about 99% amino acid sequence identity with afill-length native sequence PRO polypeptide sequence as disclosedherein, a PRO polypeptide sequence lacking the signal peptide asdisclosed herein, an extracellular domain of a PRO polypeptide, with orwithout the signal peptide, as disclosed herein or any otherspecifically defined fragment of a full-length PRO polypeptide sequenceas disclosed herein. Ordinarily, PRO variant polypeptides are at leastabout 10 amino acids in length, often at least about 20 amino acids inlength, more often at least about 30 amino acids in length, more oftenat least about 40 amino acids in length, more often at least about 50amino acids in length, more often at least about 60 amino acids inlength, more often at least about 70 amino acids in length, more oftenat least about 80 amino acids in length, more often at least about 90amino acids in length, more often at least about 100 amino acids inlength, more often at least about 150 amino acids in length, more oftenat least about 200 amino acids in length, more often at least about 300amino acids in length, or more. “Percent (%) amino acid sequenceidentity” with respect to the PRO polypeptide sequences identifiedherein is defined as the percentage of amino acid residues in acandidate sequence that are identical with the amino acid residues inthe specific PRO polypeptide sequence, after aligning the sequences andintroducing gaps, if necessary, to achieve the maximum percent sequenceidentity, and not considering any conservative substitutions as part ofthe sequence identity. Alignment for purposes of determining percentamino acid sequence identity can be achieved in various ways that arewithin the skill in the art, for instance, using publicly availablecomputer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR)software. Those skilled in the art can determine appropriate parametersfor measuring alignment, including any algorithms needed to achievemaximal alignment over the full length of the sequences being compared.For purposes herein, however, % amino acid sequence identity values aregenerated using the sequence comparison computer program ALIGN-2,wherein the complete source code for the ALIGN-2 program is provided inTable 1 below. The ALIGN-2 sequence comparison computer program wasauthored by Genentech, Inc. and the source code shown in Table 1 belowhas been filed with user documentation in the U.S. Copyright Office,Washington D.C., 20559, where it is registered under U.S. CopyrightRegistration No. TXU510087. The ALIGN-2 program is publicly availablethrough Genentech, Inc., South San Francisco, Calif. or may be compiledfrom the source code provided in Table 1 below. The ALIGN-2 programshould be compiled for use on a UNIX operating system, preferablydigital UNIX V4.0D. All sequence comparison parameters are set by theALIGN-2 program and do not vary.

[2918] In situations where ALIGN-2 is employed for amino acid sequencecomparisons, the % amino acid sequence identity of a given amino acidsequence A to, with, or against a given amino acid sequence B (which canalternatively be phrased as a given amino acid sequence A that has orcomprises a certain % amino acid sequence identity to, with, or againsta given amino acid sequence B) is calculated as follows:

100 times the fraction {fraction (X/Y)}

[2919] where X is the number of amino acid residues scored as identicalmatches by the sequence alignment program ALIGN-2 in that program'salignment of A and B, and where Y is the total number of amino acidresidues in B. It will be appreciated that where the length of aminoacid sequence A is not equal to the length of amino acid sequence B, the% amino acid sequence identity of A to B will not equal the % amino acidsequence identity of B to A. As examples of % amino acid sequenceidentity calculations using this method, Tables 2 and 3 demonstrate howto calculate the % amino acid sequence identity of the amino acidsequence designated “Comparison Protein” to the amino acid sequencedesignated “PRO”, wherein “PRO” represents the amino acid sequence of ahypothetical PRO polypeptide of interest, “Comparison Protein”represents the amino acid sequence of a polypeptide against which the“PRO” polypeptide of interest is being compared, and “X, “Y” and “Z”each represent different hypothetical amino acid residues.

[2920] Unless specifically stated otherwise, all % amino acid sequenceidentity values used herein are obtained as described in the immediatelypreceding paragraph using the ALIGN-2 computer program. However, % aminoacid sequence identity values may also be obtained as described below byusing the WU-BLAST-2 computer program (Altschul et al., Methods inEnzymology 266:460-480 (1996)). Most of the WU-BLAST-2 search parametersare set to the default values. Those not set to default values, i.e.,the adjustable parameters, are set with the following values: overlapspan=1, overlap fraction=0.125, word threshold (T)=11, and scoringmatrix=BLOSUM62. When WU-BLAST-2 is employed, a % amino acid sequenceidentity value is determined by dividing (a) the number of matchingidentical amino acid residues between the amino acid sequence of the PROpolypeptide of interest having a sequence derived from the native PROpolypeptide and the comparison amino acid sequence of interest (i.e.,the sequence against which the PRO polypeptide of interest is beingcompared which may be a PRO variant polypeptide) as determined byWU-BLAST-2 by (b) the total number of amino acid residues of the PROpolypeptide of interest. For example, in the statement “a polypeptidecomprising an the amino acid sequence A which has or having at least 80%amino acid sequence identity to the amino acid sequence B”, the aminoacid sequence A is the comparison amino acid sequence of interest andthe amino acid sequence B is the amino acid sequence of the PROpolypeptide of interest.

[2921] Percent amino acid sequence identity may also be determined usingthe sequence comparison program NCBI-BLAST2 (Altschul et al., NucleicAcids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparisonprogram may be downloaded from http://www.ncbi.nlm.nih.gov. NCBI-BLAST2uses several search parameters, wherein all of those search parametersare set to default values including, for example, unmask=yes,strand=all, expected occurrences=10, minimum low complexity length=1515,multi-pass e-value=0.01, constant for multi-pass=25, dropoff for finalgapped alignment=25 and scoring matrix=BLOSUM62.

[2922] In situations where NCBI-BLAST2 is employed for amino acidsequence comparisons, the % amino acid sequence identity of a givenamino acid sequence A to, with, or against a given amino acid sequence B(which can alternatively be phrased as a given amino acid sequence Athat has or comprises a certain % amino acid sequence identity to, with,or against a given amino acid sequence B) is calculated as follows:

100 times the fraction {fraction (X/Y)}

[2923] where X is the number of amino acid residues scored as identicalmatches by the sequence alignment program NCBI-BLAST2 in that program'salignment of A and B, and where Y is the total number of amino acidresidues in B. It will be appreciated that where the length of aminoacid sequence A is not equal to the length of amino acid sequence B, the% amino acid sequence identity of A to B will not equal the % amino acidsequence identity of B to A.

[2924] “PRO variant polynucleotide” or “PRO variant nucleic acidsequence” means a nucleic acid molecule which encodes an active PROpolypeptide as defined below and which has at least about 80% nucleicacid sequence identity with a nucleotide acid sequence encoding afull-length native sequence PRO polypeptide sequence as disclosedherein, a full-length native sequence PRO polypeptide sequence lackingthe signal peptide as disclosed herein, an extracellular domain of a PROpolypeptide, with or without the signal peptide, as disclosed herein orany other fragment of a full-length PRO polypeptide sequence asdisclosed herein. Ordinarily, a PRO variant polynucleotide will have atleast about 80% nucleic acid sequence identity, more preferably at leastabout 81% nucleic acid sequence identity, more preferably at least about82% nucleic acid sequence identity, more preferably at least about 83%nucleic acid sequence identity, more preferably at least about 84%nucleic acid sequence identity, more preferably at least about 85%nucleic acid sequence identity, more preferably at least about 86%nucleic acid sequence identity, more preferably at least about 87%nucleic acid sequence identity, more preferably at least about 88%nucleic acid sequence identity, more preferably at least about 89%nucleic acid sequence identity, more preferably at least about 90%nucleic acid sequence identity, more preferably at least about 91%nucleic acid sequence identity, more preferably at least about 92%nucleic acid sequence identity, more preferably at least about 93%nucleic acid sequence identity, more preferably at least about 94%nucleic acid sequence identity, more preferably at least about 95%nucleic acid sequence identity, more preferably at least about 96%nucleic acid sequence identity, more preferably at least about 97%nucleic acid sequence identity, more preferably at least about 98%nucleic acid sequence identity and yet more preferably at least about99% nucleic acid sequence identity wit h a nucleic acid sequenceencoding a full-length native sequence PRO polypeptide sequence asdisclosed herein, a full-length native sequence PRO polypeptide sequencelacking the signal peptide as disclosed herein, an extracellular domainof a PRO polypeptide, with or without the signal sequence, as disclosedherein or any other fragment of a full-length PRO polypeptide sequenceas disclosed herein. Variants do not encompass the native nucleotidesequence.

[2925] Ordinarily, PRO variant polynucleotides are at least about 30nucleotides in length, often at least about 60 nucleotides in length,more often at least about 90 nucleotides in length, more often at leastabout 120 nucleotides in length, more often at least about 150nucleotides in length , more often at least about 180 nucleotides inlength, more often at least about 210 nucleotides in length, more oftenat least about 240 nucleotides in length, more often at least about 270nucleotides in length, more often at least about 300 nucleotides inlength, more often at least about 450 nucleotides in length, more oftenat least about 600 nucleotides in length, more often at least about 900nucleotides in length, or more.

[2926] “Percent (%) nucleic acid sequence identity” with respect toPRO-encoding nucleic acid sequences identified herein is defined as thepercentage of nucleotides in a candidate sequence that are identicalwith the nucleotides in the PRO nucleic acid sequence of interest, afteraligning the sequences and introducing gaps, if necessary, to achievethe maximum percent sequence identity. Alignment for purposes ofdetermining percent nucleic acid sequence identity can be achieved invarious ways that are within the skill in the art, for instance, usingpublicly available computer software such as BLAST, BLAST-2, ALIGN orMegalign (DNASTAR) software. For purposes herein, however, % nucleicacid sequence identity values are generated using the sequencecomparison computer program ALIGN-2, wherein the complete source codefor the ALIGN-2 program is provided in Table 1 below. The ALIGN-2sequence comparison computer program was authored by Genentech, Inc. andthe source code shown in Table 1 below has been filed with userdocumentation in the U.S. Copyright Office, Washington D.C., 20559,where it is registered under U.S. Copyright Registration No. TXU510087.The ALIGN-2 program is publicly available through Genentech, Inc., SouthSan Francisco, Calif. or may be compiled from the source code providedin Table 1 below. The ALIGN-2 program should be compiled for use on aUNIX operating system, preferably digital UNIX V4.0D. All sequencecomparison parameters are set by the ALIGN-2 program and do not vary.

[2927] In situations where ALIGN-2 is employed for nucleic acid sequencecomparisons, the % nucleic acid sequence identity of a given nucleicacid sequence C to, with, or against a given nucleic acid sequence D(which can alternatively be phrased as a given nucleic acid sequence Cthat has or comprises a certain % nucleic acid sequence identity to,with, or against a given nucleic acid sequence D) is calculated asfollows:

100 times the fraction {fraction (W/Z)}

[2928] where W is the number of nucleotides scored as identical matchesby the sequence alignment program ALIGN-2 in that program's alignment ofC and D, and where Z is the total number of nucleotides in D. It will beappreciated that where the length of nucleic acid sequence C is notequal to the length of nucleic acid sequence D, the % nucleic acidsequence identity of C to D will not equal the % nucleic acid sequenceidentity of D to C. As examples of % nucleic acid sequence identitycalculations, Tables 4 and 5, demonstrate how to calculate the % nucleicacid sequence identity of the nucleic acid sequence designated“Comparison DNA” to the nucleic acid sequence designated “PRO-DNA”,wherein “PRO-DNA” represents a hypothetical PRO-encoding nucleic acidsequence of interest, “Comparison DNA” represents the nucleotidesequence of a nucleic acid molecule against which the “PRO-DNA” nucleicacid molecule of interest is being compared, and “N, “L” and “V” eachrepresent different hypothetical nucleotides.

[2929] Unless specifically stated otherwise, all % nucleic acid sequenceidentity values used herein are obtained as described in the immediatelypreceding paragraph using the ALIGN-2 computer program. However, %nucleic acid sequence identity values may also be obtained as describedbelow by using the WU-BLAST-2 computer program (Altschul et al., Methodsin Enzymology 266:460-480 (1996)). Most of the WU-BLAST-2 searchparameters are set to the default values. Those not set to defaultvalues, i.e., the adjustable parameters, are set with the followingvalues: overlap span=1, overlap fraction=0.125, word threshold (T)=11,and scoring matrix=BLOSUM62. When WU-BLAST-2 is employed, a % nucleicacid sequence identity value is determined by dividing (a) the number ofmatching identical nucleotides between the nucleic acid sequence of thePRO polypeptide-encoding nucleic acid molecule of interest having asequence derived from the native sequence PRO polypeptide-encodingnucleic acid and the comparison nucleic acid molecule of interest (i.e.,the sequence against which the PRO polypeptide-encoding nucleic acidmolecule of interest is being compared which may be a variant PROpolynucleotide) as determined by WU-BLAST-2 by (b) the total number ofnucleotides of the PRO polypeptide-encoding nucleic acid molecule ofinterest. For example, in the statement “an isolated nucleic acidmolecule comprising a nucleic acid sequence A which has or having atleast 80% nucleic acid sequence identity to the nucleic acid sequenceB”, the nucleic acid sequence A is the comparison nucleic acid moleculeof interest and the nucleic acid sequence B is the nucleic acid sequenceof the PRO polypeptide-encoding nucleic acid molecule of interest.

[2930] Percent nucleic acid sequence identity may also be determinedusing the sequence comparison program NCBI-BLAST2 (Altschul et al.,Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequencecomparison program may be downloaded from http://www.ncbi.nlm.nih.gov.NCBI-BLAST2 uses several search parameters, wherein all of those searchparameters are set to default values including, for example, unmask=yes,strand=all, expected occurrences=10, minimum low complexity length=15/5,multi-pass e-value=0.01, constant for multi-pass=25, dropoff for finalgapped alignment=25 and scoring matrix BLOSUM62.

[2931] In situations where NCBI-BLAST2 is employed for sequencecomparisons, the % nucleic acid sequence identity of a given nucleicacid sequence C to, with, or against a given nucleic acid sequence D(which can alternatively be phrased as a given nucleic acid sequence Cthat has or comprises a certain % nucleic acid sequence identity to,with, or against a given nucleic acid sequence D) is calculated asfollows:

100 times the fraction {fraction (W/Z)}

[2932] where W is the number of nucleotides scored as identical matchesby the sequence alignment program NCBI-BLAST2 in that program'salignment of C and D, and where Z is the total number of nucleotides inD. It will be appreciated that where the length of nucleic acid sequenceC is not equal to the length of nucleic acid sequence D, the % nucleicacid sequence identity of C to D will not equal the % nucleic acidsequence identity of D to C.

[2933] In other embodiments, PRO variant polynucleotides are nucleicacid molecules that encode an active PRO polypeptide and which arecapable of hybridizing, preferably under stringent hybridization andwash conditions, to nucleotide sequences encoding a full-length PROpolypeptide as disclosed herein. PRO variant polypeptides may be thosethat are encoded by a PRO variant polynucleotide.

[2934] The term “positives”, in the context of sequence comparisonperformed as described above, includes residues in the sequencescompared that are not identical but have similar properties (e.g. as aresult of conservative substitutions, see Table 6 below). For purposesherein, the % value of positives is determined by dividing (a) thenumber of amino acid residues scoring a positive value between the PROpolypeptide amino acid sequence of interest having a sequence derivedfrom the native PRO polypeptide sequence and the comparison amino acidsequence of interest (i.e., the amino acid sequence against which thePRO polypeptide sequence is being compared) as determined in theBLOSUM62 matrix of WU-BLAST-2 by (b) the total number of amino acidresidues of the PRO polypeptide of interest.

[2935] Unless specifically stated otherwise, the % value of positives iscalculated as described in the immediately preceding paragraph. However,in the context of the amino acid sequence identity comparisons performedas described for ALIGN-2 and NCBI-BLAST-2 above, includes amino acidresidues in the sequences compared that are not only identical, but alsothose that have similar properties. Amino acid residues that score apositive value to an amino acid residue of interest are those that areeither identical to the amino acid residue of interest or are apreferred substitution (as defined in Table 6 below) of the amino acidresidue of interest.

[2936] For amino acid sequence comparisons using ALIGN-2 or NCBI-BLAST2,the % value of positives of a given amino acid sequence A to, with, oragainst a given amino acid sequence B (which can alternatively bephrased as a given amino acid sequence A that has or comprises a certain% positives to, with, or against a given amino acid sequence B) iscalculated as follows:

100 times the fraction {fraction (X/Y)}

[2937] where X is the number of amino acid residues scoring a positivevalue as defined above by the sequence alignment program ALIGN-2 orNCBI-BLAST2 in that program's alignment of A and B, and where Y is thetotal number of amino acid residues in B. It will be appreciated thatwhere the length of amino acid sequence A is not equal to the length ofamino acid sequence B, the % positives of A to B will not equal the %positives of B to A.

[2938] “Isolated,” when used to describe the various polypeptidesdisclosed herein, means polypeptide that has been identified andseparated and/or recovered from a component of its natural environment.Contaminant components of its natural environment are materials thatwould typically interfere with diagnostic or therapeutic uses for thepolypeptide, and may include enzymes, hormones, and other proteinaceousor non-proteinaceous solutes. In preferred embodiments, the polypeptidewill be purified (1) to a degree sufficient to obtain at least 15residues of N-terminal or internal amino acid sequence by use of aspinning cup sequenator, or (2) to homogeneity by SDS-PAGE undernon-reducing or reducing conditions using Coomassie blue or, preferably,silver stain. Isolated polypeptide includes polypeptide in situ withinrecombinant cells, since at least one component of the PRO polypeptidenatural environment will not be present. Ordinarily, however, isolatedpolypeptide will be prepared by at least one purification step.

[2939] An “isolated” PRO polypeptide-encoding nucleic acid or otherpolypeptide-encoding nucleic acid is a nucleic acid molecule that isidentified and separated from at least one contaminant nucleic acidmolecule with which it is ordinarily associated in the natural source ofthe polypeptide-encoding nucleic acid. An isolated polypeptide-encodingnucleic acid molecule is other than in the form or setting in which itis found in nature. Isolated polypeptide-encoding nucleic acid moleculestherefore are distinguished from the specific polypeptide-encodingnucleic acid molecule as it exists in natural cells. However, anisolated polypeptide-encoding nucleic acid molecule includespolypeptide-encoding nucleic acid molecules contained in cells thatordinarily express the polypeptide where, for example, the nucleic acidmolecule is in a chromosomal location different from that of naturalcells.

[2940] The term “control sequences” refers to DNA sequences necessaryfor the expression of an operably linked coding sequence in a particularhost organism. The control sequences that are suitable for prokaryotes,for example, include a promoter, optionally an operator sequence, and aribosome binding site. Eukaryotic cells are known to utilize promoters,polyadenylation signals, and enhancers.

[2941] Nucleic acid is “operably linked” when it is placed into afunctional relationship with another nucleic acid sequence. For example,DNA for a presequence or secretory leader is operably linked to DNA fora polypeptide if it is expressed as a preprotein that participates inthe secretion of the polypeptide; a promoter or enhancer is operablylinked to a coding sequence if it affects the transcription of thesequence; or a ribosome binding site is operably linked to a codingsequence if it is positioned so as to facilitate translation. Generally,“operably linked” means that the DNA sequences being linked arecontiguous, and, in the case of a secretory leader, contiguous and inreading phase. However, enhancers do not have to be contiguous. Linkingis accomplished by ligation at convenient restriction sites. If suchsites do not exist, the synthetic oligonucleotide adaptors or linkersare used in accordance with conventional practice.

[2942] The term “antibody” is used in the broadest sense andspecifically covers, for example, single anti-PRO monoclonal antibodies(including agonist, antagonist, and neutralizing antibodies), anti-PROantibody compositions with polyepitopic specificity, single chainanti-PRO antibodies, and fragments of anti-PRO antibodies (see below).The term “monoclonal antibody” as used herein refers to an antibodyobtained from a population of substantially homogeneous antibodies,i.e., the individual antibodies comprising the population are identicalexcept for possible naturally-occurring mutations that may be present inminor amounts.

[2943] “Stringency” of hybridization reactions is readily determinableby one of ordinary skill in the art, and generally is an empiricalcalculation dependent upon probe length, washing temperature, and saltconcentration. In general, longer probes require higher temperatures forproper annealing, while shorter probes need lower temperatures.Hybridization generally depends on the ability of denatured DNA toreanneal when complementary strands are present in an environment belowtheir melting temperature. The higher the degree of desired homologybetween the probe and hybridizable sequence, the higher the relativetemperature which can be used. As a result, it follows that higherrelative temperatures would tend to make the reaction conditions morestringent, while lower temperatures less so. For additional details andexplanation of stringency of hybridization reactions, see Ausubel etal., Current Protocols in Molecular Biology, Wiley IntersciencePublishers, (1995).

[2944] “Stringent conditions” or “high stringency conditions”, asdefined herein, may be identified by those that: (1) employ low ionicstrength and high temperature for washing, for example 0.015 M sodiumchloride/0.0015 M sodium citrate/0. 1% sodium dodecyl sulfate at 50° C.;(2) employ during hybridization a denaturing agent, such as formamide,for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1%Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3)employ 50% formamide, 5× SSC (0.75 M NaCl, 0.075 M sodium citrate), 50mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5× Denhardt'ssolution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10%dextran sulfate at 42° C., with washes at 42° C. in 0.2× SSC (sodiumchloride/sodium citrate) and 50% formamide at 55° C., followed by ahigh-stringency wash consisting of 0.1× SSC containing EDTA at 55° C.

[2945] “Moderately stringent conditions” may be identified as describedby Sambrook et al., Molecular Cloning: A Laboratory Manual, New York:Cold Spring Harbor Press, 1989, and include the use of washing solutionand hybridization conditions (e.g., temperature, ionic strength and%SDS) less stringent that those described above. An example ofmoderately stringent conditions is overnight incubation at 37° C. in asolution comprising: 20% formamide, 5× SSC (150 mM NaCl, 15 mM trisodiumcitrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10%dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA,followed by washing the filters in 1× SSC at about 37-50° C. The skilledartisan will recognize how to adjust the temperature, ionic strength,etc. as necessary to accommodate factors such as probe length and thelike.

[2946] The term “epitope tagged” when used herein refers to a chimericpolypeptide comprising a PRO polypeptide fused to a “tag polypeptide”.The tag polypeptide has enough residues to provide an epitope againstwhich an antibody can be made, yet is short enough such that it does notinterfere with activity of the polypeptide to which it is fused. The tagpolypeptide preferably also is fairly unique so that the antibody doesnot substantially cross-react with other epitopes. Suitable tagpolypeptides generally have at least six amino acid residues and usuallybetween about 8 and 50 amino acid residues (preferably, between about 10and 20 amino acid residues).

[2947] As used herein, the term “immunoadhesin” designates antibody-likemolecules which combine the binding specificity of a heterologousprotein (an “adhesin”) with the effector functions of immunoglobulinconstant domains. Structurally, the immunoadhesins comprise a fusion ofan amino acid sequence with the desired binding specificity which isother than the antigen recognition and binding site of an antibody(i.e., is “heterologous”), and an immunoglobulin constant domainsequence. The adhesin part of an immunoadhesin molecule typically is acontiguous amino acid sequence comprising at least the binding site of areceptor or a ligand. The immunoglobulin constant domain sequence in theimmunoadhesin may be obtained from any immunoglobulin, such as IgG-1,IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE,IgD or IgM.

[2948] “Active” or “activity” for the purposes herein refers to form(s)of a PRO polypeptide which retain a biological and/or an immunologicalactivity of native or naturally-occurring PRO, wherein “biological”activity refers to a biological function (either inhibitory orstimulatory) caused by a native or naturally-occurring PRO other thanthe ability to induce the production of an antibody against an antigenicepitope possessed by a native or naturally-occurring PRO and an“immunological” activity refers to the ability to induce the productionof an antibody against an antigenic epitope possessed by a native ornaturally-occurring PRO.

[2949] The term “antagonist” is used in the broadest sense, and includesany molecule that partially or fully blocks, inhibits, or neutralizes abiological activity of a native PRO polypeptide disclosed herein. In asimilar manner, the term “agonist” is used in the broadest sense andincludes any molecule that mimics a biological activity of a native PROpolypeptide disclosed herein. Suitable agonist or antagonist moleculesspecifically include agonist or antagonist antibodies or antibodyfragments, fragments or amino acid sequence variants of native PROpolypeptides, peptides, antisense oligonucleotides, small organicmolecules, etc. Methods for identifying agonists or antagonists of a PROpolypeptide may comprise contacting a PRO polypeptide with a candidateagonist or antagonist molecule and measuring a detectable change in oneor more biological activities normally associated with the PROpolypeptide.

[2950] “Treatment” refers to both therapeutic treatment and prophylacticor preventative measures, wherein the object is to prevent or slow down(lessen) the targeted pathologic condition or disorder. Those in need oftreatment include those already with the disorder as well as those proneto have the disorder or those in whom the disorder is to be prevented.

[2951] “Chronic” administration refers to administration of the agent(s)in a continuous mode as opposed to an acute mode, so as to maintain theinitial therapeutic effect (activity) for an extended period of time.“Intermittent” administration is treatment that is not consecutivelydone without interruption, but rather is cyclic in nature.

[2952] “Mammal” for purposes of treatment refers to any animalclassified as a mammal, including humans, domestic and farm animals, andzoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep,pigs, goats, rabbits, etc. Preferably, the mammal is human.

[2953] Administration “in combination with” one or more furthertherapeutic agents includes simultaneous (concurrent) and consecutiveadministration in any order.

[2954] “Carriers” as used herein include pharmaceutically acceptablecarriers, excipients, or stabilizers which are nontoxic to the cell ormammal being exposed thereto at the dosages and concentrations employed.Often the physiologically acceptable carrier is an aqueous pH bufferedsolution. Examples of physiologically acceptable carriers includebuffers such as phosphate, citrate, and other organic acids;antioxidants including ascorbic acid; low molecular weight (less thanabout 10 residues) polypeptide; proteins, such as serum albumin,gelatin, or immunoglobulins; hydrophilic polymers such aspolyvinylpyrrolidone; amino acids such as glycine, glutamine,asparagine, arginine or lysine; monosaccharides, disaccharides, andother carbohydrates including glucose, mannose, or dextrins; chelatingagents such as EDTA; sugar alcohols such as mannitol or sorbitol;salt-forming counterions such as sodium; and/or nonionic surfactantssuch as TWEEN™, polyethylene glycol (PEG), and PLURONICS™.

[2955] “Antibody fragments” comprise a portion of an intact antibody,preferably the antigen binding or variable region of the intactantibody. Examples of antibody fragments include Fab, Fab′, F(ab′)₂, andFv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng.8(10): 1057-1062 [1995]); single-chain antibody molecules; andmultispecific antibodies formed from antibody fragments.

[2956] Papain digestion of antibodies produces two identicalantigen-binding fragments, called “Fab” fragments, each with a singleantigen-binding site, and a residual “Fc” fragment, a designationreflecting the ability to crystallize readily. Pepsin treatment yieldsan F(ab′)₂ fragment that has two antigen-combining sites and is stillcapable of cross-linking antigen.

[2957] “Fv” is the minimum antibody fragment which contains a completeantigen-recognition and -binding site. This region consists of a dimerof one heavy- and one light-chain variable domain in tight, non-covalentassociation. It is in this configuration that the three CDRs of eachvariable domain interact to define an antigen-binding site on thesurface of the V_(H)-V_(L) dimer. Collectively, the six CDRs conferantigen-binding specificity to the antibody. However, even a singlevariable domain (or half of an Fv comprising only three CDRs specificfor an antigen) has the ability to recognize and bind antigen, althoughat a lower affinity than the entire binding site.

[2958] The Fab fragment also contains the constant domain of the lightchain and the first constant domain (CH1) of the heavy chain. Fabfragments differ from Fab′ fragments by the addition of a few residuesat the carboxy terminus of the heavy chain CH 1 domain including one ormore cysteines from the antibody hinge region. Fab′-SH is thedesignation herein for Fab′ in which the cysteine residue(s) of theconstant domains bear a free thiol group. F(ab′)₂ antibody fragmentsoriginally were produced as pairs of Fab′ fragments which have hingecysteines between them. Other chemical couplings of antibody fragmentsare also known.

[2959] The “light chains” of antibodies (immunoglobulins) from anyvertebrate species can be assigned to one of two clearly distinct types,called kappa and lambda, based on the amino acid sequences of theirconstant domains.

[2960] Depending on the amino acid sequence of the constant domain oftheir heavy chains, immunoglobulins can be assigned to differentclasses. There are five major classes of immunoglobulins: IgA, IgD, IgE,IgG, and IgM, and several of these may be further divided intosubclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA, and IgA2.

[2961] “Single-chain Fv” or “sFv” antibody fragments comprise the V_(H)and V_(L) domains of antibody, wherein these domains are present in asingle polypeptide chain. Preferably, the Fv polypeptide furthercomprises a polypeptide linker between the V_(H) and V_(L) domains whichenables the sFv to form the desired structure for antigen binding. For areview of sFv, see Pluckthun in The Pharmacology of MonoclonalAntibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, NewYork, pp. 269-315 (1994).

[2962] The term “diabodies” refers to small antibody fragments with twoantigen-binding sites, which fragments comprise a heavy-chain variabledomain (V_(H)) connected to a light-chain variable domain (V_(L)) in thesame polypeptide chain (V_(H)-V_(L)). By using a linker that is tooshort to allow pairing between the two domains on the same chain, thedomains are forced to pair with the complementary domains of anotherchain and create two antigen-binding sites. Diabodies are described morefully in, for example, EP 404,097; WO 93/11161; and Hollinger et al.,Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[2963] An “isolated” antibody is one which has been identified andseparated and/or recovered from a component of its natural environment.Contaminant components of its natural environment are materials whichwould interfere with diagnostic or therapeutic uses for the antibody,and may include enzymes, hormones, and other proteinaceous ornonproteinaceous solutes. In preferred embodiments, the antibody will bepurified (1) to greater than 95% by weight of antibody as determined bythe Lowry method, and most preferably more than 99% by weight, (2) to adegree sufficient to obtain at least 15 residues of N-terminal orinternal amino acid sequence by use of a spinning cup sequenator, or (3)to homogeneity by SDS-PAGE under reducing or nonreducing conditionsusing Coomassie blue or, preferably, silver stain. Isolated antibodyincludes the antibody in situ within recombinant cells since at leastone component of the antibody's natural environment will not be present.Ordinarily, however, isolated antibody will be prepared by at least onepurification step.

[2964] The word “label” when used herein refers to a detectable compoundor composition which is conjugated directly or indirectly to theantibody so as to generate a “labeled” antibody. The label may bedetectable by itself (e.g. radioisotope labels or fluorescent labels)or, in the case of an enzymatic label, may catalyze chemical alterationof a substrate compound or composition which is detectable.

[2965] By “solid phase” is meant a non-aqueous matrix to which theantibody of the present invention can adhere. Examples of solid phasesencompassed herein include those formed partially or entirely of glass(e.g., controlled pore glass), polysaccharides (e.g., agarose),polyacrylamides, polystyrene, polyvinyl alcohol and silicones. Incertain embodiments, depending on the context, the solid phase cancomprise the well of an assay plate; in others it is a purificationcolumn (e.g., an affinity chromatography column). This term alsoincludes a discontinuous solid phase of discrete particles, such asthose described in U.S. Pat. No. 4,275,149.

[2966] A “liposome” is a small vesicle composed of various types oflipids, phospholipids and/or surfactant which is useful for delivery ofa drug (such as a PRO polypeptide or antibody thereto) to a mammal. Thecomponents of the liposome are commonly arranged in a bilayer formation,similar to the lipid arrangement of biological membranes.

[2967] A “small molecule” is defined herein to have a molecular weightbelow about 500 Daltons. TABLE 1 /*  *  * C-C increased from 12 to 15  *Z is average of EQ  * B is average of ND  * match with stop is _M;stop-stop = 0; J (joker) match = 0  */ #define _M −8 /* value of a matchwith a stop */ int _day[26][26] = { /*  A B C D E F G H I J K L M N O PQ R S T U V W X Y Z */ /* A */ {2, 0, −2, 0, 0, −4, 1, −1, −1, 0, −1,−2, −1, 0, _M, 1, 0, −2, 1, 1, 0, 0, −6, 0, −3, 0}, /* B */ {0, 3, −4,3, 2, −5, 0, 1, −2, 0, 0, −3, −2, 2, _M, −1, 1, 0, 0, 0, 0, −2, −5, 0,−3, 1}, /* C */ {−2, −4, 15, −5, −5, −4, −3, −3, −2, 0, −5, −6, −5, −4,_M, −3, −5, −4, 0, −2, 0, −2, −8, 0, 0, −5}, /* D */ {0, 3, −5, 4, 3,−6, 1, 1, −2, 0, 0, −4, −3, 2, _M, −1, 2, −1, 0, 0, 0, −2, −7, 0, −4,2}, /* E */ {0, 2, −5, 3, 4, −5, 0, 1, −2, 0, 0, −3, −2, 1, _M, −1, 2,−1, 0, 0, 0, −2, −7, 0, −4, 3}, /* F */ {−4, −5, −4, −6, −5, 9, −5, −2,1, 0, −5, 2, 0, −4, _M, −5, −5, −4, −3, −3, 0, −1, 0, 0, 7, −5}, /* G */{1, 0, −3, 1, 0, −5, 5, −2, −3, 0, −2, −4, −3, 0, _M, −1, −1, −3, 1, 0,0, −1, −7, 0, −5, 0}, /* H */ {−1, 1, −3, 1, 1, −2, −2, 6, −2, 0, 0, −2,−2, 2, _M, 0, 3, 2, −1, −1, 0, −2, −3, 0, 0, 2}, /* I */ {−1, −2, −2,−2, −2, 1, −3, −2, 5, 0, −2, 2, 2, −2, _M, −2, −2, −2, −1, 0, 0, 4, −5,0, −1, −2}, /* J */ {0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, _M, 0, 0,0, 0, 0, 0, 0, 0, 0, 0, 0}, /* K */ {−1, 0, −5, 0, 0, −5, −2, 0, −2, 0,5, −3, 0, 1, _M, −1, 1, 3, 0, 0, 0, −2, −3, 0, −4, 0}, /* L */ {−2, −3,−6, −4, −3, 2, −4, −2, 2, 0, −3, 6, 4, −3, _M, −3, −2, −3, −3 , −1, 0,2, −2, 0, −1, −2} /* M */ {−1, −2, −5, −3, −2, 0, −3, −2, 2, 0, 0, 4, 6,−2, _M, −2, −1, 0, −2, −1, 0, 2, −4, 0, −2, −1}, /* N */ {0, 2, −4, 2,1, −4, 0, 2, −2, 0, 1, −3, −2, 2, _M, −1, 1, 0, 1, 0, 0, −2, −4, 0, −2,1}, /* O */ {_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,0,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,}, /* P */ {1, −1, −3, −1, −1, −5,−1, 0, −2, 0, −1, −3, −2, −1,_M, 6, 0, 0, 1, 0, 0, −1, −6, 0, −5, 0}, /*Q */ {0, 1, −5, 2, 2, −5, −1, 3, −2, 0, 1, −2, −1, 1, _M, 0, 4, 1, −1,−1, 0, −2, −5, 0, −4, 3}, /* R */ {−2, 0, −4, −1, −1, −4, −3, 2, −2, 0,3, −3, 0, 0, _M, 0, 1, 6, 0, −1, 0, −2, 2, 0, −4, 0}, /* S */ {1, 0, 0,0, 0, −3, 1, −1, −1, 0, 0, −3, −2, 1, _M, 1, −1, 0, 2, 1, 0, −1, −2, 0,−3, 0}, /* T */ {1, 0, −2, 0, 0, −3, 0, −1, 0, 0, 0, −1, −1, 0, _M, 0,−1, −1, 1, 3, 0, 0, −5, 0, −3, 0}, /* U */ {0, 0, 0, 0, 0, 0, 0, 0, 0,0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0}, /* V */ {0, −2, −2,−2, −2, −1, −1, −2, 4, 0, −2, 2, 2, −2,_M, −1, −2, −2, −1, 0, 0, 4, −6,0, −2, −2}, /* W */ {−6, −5, −8, −7, −7, 0, −7, −3, −5, 0, −3, −2, −4,−4,_M, −6, −5, 2, −2, −5, 0, −6, 17, 0, 0, −6}, /* X */ {0, 0, 0, 0, 0,0, 0, 0, 0, 0, 0, 0, 0, 0, _M, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0}, /* Y */{−3, −3, 0, −4, −4, 7, −5, 0, −1, 0, −4, −1, −2, −2, _M, −5, −4, −4, −3,−3, 0, −2, 0, 0, 10, −4}, /* Z */ {0, 1, −5, 2, 3, −5, 0, 2, −2, 0, 0,−2, −1, 1,_M, 0, 3, 0, 0, 0, 0, −2, −6, 0, −4, 4}, }; /*  */ #include<stdio.h> #include <ctype.h> #define MAXJMP  16 /* max jumps in a diag*/ #define MAXGAP  24 /* don't continue to penalize gaps larger thanthis */ #define JMPS 1024 /* max jmps in an path */ #define MX   4 /*save if there's at least MX-1 bases since last jmp */ #define DMAT   3/* value of matching bases */ #define DMIS   0 /* penalty for mismatchedbases */ #define DINS0   8 /* penalty for a gap */ #define DINS1   1 /*penalty per base */ #define PINS0   8 /* penalty for a gap */ #definePINS1   4 /* penalty per residue */ struct jmp { short n[MAXJMP]; /*size of jmp (neg for dely) */ unsigned short x[MAXJMP]; /* base no. ofjmp in seq x */ /* limits seq to 2{circumflex over ( )}16 −1 */ };struct diag { int score; /* score at last jmp */ long offset; /* offsetof prev block */ short ijmp; /* current jmp index */ struct jmp jp; /*list of jmps */ }; struct path { int spc; /* number of leading spaces */short n[JMPS]; /* size of jmp (gap) */ int x[JMPS]; /* loc of jmp (lastelem before gap) */ }; char *ofile; /* output file name */ char*namex[2]; /* seq names: getseqs() */ char *prog; /* prog name for errmsgs */ char *seqx[2];   /* seqs: getseqs() */ int dmax; /* best diag:nw() */ int dmax0; /* final diag */ int dna; /* set if dna: main() */int endgaps; /* set if penalizing end gaps */ int gapx, gapy; /* totalgaps in seqs */ int len0, len1; /* seq lens */ int ngapx, ngapy; /*total size of gaps */ int smax; /* max score: nw() */ int *xbm; /*bitmap for matching */ long offset; /* current offset in jmp file */struct diag *dx; /* holds diagonals */ struct path pp[2]; /* holds pathfor seqs */ char *calloc(), *malloc(), *index(), *strcpy(); char*getseq(), *g_calloc(); /* Needleman-Wunsch alignment program  *  *usage: progs file1 file2  * where file1 and file2 are two dna or twoprotein sequences.  * The sequences can be in upper- or lower-case anmay contain ambiguity  * Any lines beginning with ‘;’, ‘>’ or ‘<’ areignored  * Max file length is 65535 (limited by unsigned short x in thejmp struct)  * A sequence with ⅓ or more of its elements ACGTU isassumed to be DNA  * Output is in the file “align.out”  *  * The programmay create a tmp file in /tmp to hold info about traceback.  * Originalversion developed under BSD 4.3 on a vax 8650  */ #include “nw.h”#include “day.h” static _dbval[26] = {1,14,2,13,0,0,4,11,0,0,12,0,3,15,0,0,0,5,6,8,8,7,9,0,10,0 }; static_pbval[26] = { 1, 2|(1< <(‘D’-‘A’))|(1< <(‘N’-‘A’)), 4, 8, 16, 32, 64,128, 256, 0×FFFFFFF, 1< <10, 1< <11, 1< <12, 1< <13, 1< <14, 1< <15, 1<<16, 1< <17, 1< <18, 1< <19, 1< <20, 1< <21, 1< <22, 1< <23, 1< <24, 1<<25|(1< <(‘E’-‘A’))|(1< <(‘Q’-‘A’)) }; main(ac, av) main int ac; char*av[]; { prog = av[0]; if(ac != 3) { fprintf(stderr, “usage: %s file1file2\n”, prog); fprintf(stderr, “where file1 and file2 are two dna ortwo protein sequences.\n”); fprintf(stderr, “The sequences can be inupper- or lower-case\n”); fprintf(stderr, “Any lines beginning with ‘;’or ‘<’ are ignored\n”); fprintf(stderr, “Output is in the file\“align.out\”\n”); exit(1); } namex[0] = av[1]; namex[1] = av[2];seqx[0] = getseq(namex[0], &len0); seqx[1] = getseq(namex[1], &len1);xbm = (dna)? _dbval : _pbval; endgaps = 0; /* 1 to penalize endgaps */ofile = “align.out”; /* output file */ nw(); /* fill in the matrix, getthe possible jmps */ readjmps(); /* get the actual jmps */ print(); /*print stats, alignment */ cleanup(0); /* unlink any tmp files */ } /* dothe alignment, return best score: main()  * dna: values in Fitch andSmith, PNAS, 80, 1382-1386, 1983  * pro: PAM 250 values  * When scoresare equal, we prefer mismatches to any gap, prefer  * a new gap toextending an ongoing gap, and prefer a gap in seqx  * to a gap in seq y. */ nw() nw { char *px, *py;   /* seqs and ptrs */ int *ndely, *dely; /*keep track of dely */ int ndelx, delx; /* keep track of delx */ int*tmp; /* for swapping row0, row1 */ int mis; /* score for each type */int ins0, ins1; /* insertion penalties */ register id; /* diagonal index*/ register ij; /* jmp index */ register *col0, *col1; /* score forcurr, last row */ register xx, yy; /* index into seqs */ dx = ( structdiag *)g_calloc(“to get diags”, len0 + len1 + 1, sizeof(struct diag));ndely = (int *)g_calloc(“to get ndely”, len1 + 1, sizeof(int)); dely =(int *)g_calloc(“to get dely”, len1 + 1, sizeof(int)); col0 = (int*)g_calloc(“to get col0”, len1 + 1, sizeof(int)); col1 = (int*)g_calloc(“to get col1”, len1 + 1, sizeof(int)); ins0 = (dna)? DINS0 :PINS0; ins1 = (dna)? DINS1 : PlNS1; smax = −10000; if (endgaps) { for(col0[0] = dely[0] = −ins0, yy = 1; yy <= len1; yy++) { col0[yy] =dely[yy] = col0[yy−1] − ins1; ndely[yy] = yy; } col0[0] = 0; /* WatermanBull Math Biol 84 */ } else for (yy= 1; yy <= len1; yy++) dely[yy] =−ins0; /* fill in match matrix  */ for (px = seqx[0], xx = 1; xx <=len0; px++, xx++) { /* initialize first entry in col  */ if (endgaps) {if (xx == 1) col1[0] = delx = −(ins0 + ins1); else col1[0] = delx =col0[0] − ins1; ndelx = xx; } else { col1[0] = 0; delx = −ins0; ndelx =0; } ...nw for (py = seqx[1], yy = 1; yy <= len1; py++, yy++) { mis =col0[yy−1]; if (dna) mis + = (xbm[*px−‘A’]&xbm[*py−‘A’])? DMAT : DMIS;else mis += _day[/*px−‘A’][*py−‘A’]; /* update penalty for del in x seq; * favor new del over ongong del  * ignore MAXGAP if weighting endgaps */ if (endgaps || ndely[yy] < MAXGAP) { if (col0[yy] − ins0 >=dely[yy]) { dely[yy] = col0[yy] − (ins0+ins1); ndely[yy] = 1; } else {dely[yy] −= ins1; ndely[yy]++; } } else { if (col0[yy] − (ins0+ins1) >=dely[yy]) { dely[yy] = col0[yy] − (ins0+ins1); ndely[yy] = 1; } elsendely[yy]++; } /* update penalty for del in y seq;  * favor new del overongong del  */ if (endgaps || ndelx < MAXGAP) { if(col1[yy−1] − ins0 >=delx) { delx = col1[yy−1] − (ins0+ins1); ndelx = 1; } else { delx −=ins1; ndelx++; } } else { if (col1[yy−1] − (ins0+ins1) >= delx) { delxcol1[yy−1] − (ins0+ins1); ndelx = 1; } else ndelx++; } /* pick themaximum score; we're favoring  * mis over any del and delx over dely  */...nw id = xx − yy + len1 − 1; if (mis >= delx && mis >= dely[yy])col1[yy] = mis; else if (delx >= dely[yy]) { col1[yy] = delx; ij =dx[id].ijmp; if (dx[id].jp.n[0] && (!dna || (ndelx >= MAXJMP && xx >dx[id].jp.x[ij]+MX) || mis > dx[id].score+DINS0)) { dx[id].ijmp++; if(++ij >= MAXJMP) { writejmps(id); ij = dx[id].ijmp = 0; dx[id].offset =offset; offset += sizeof(struct jmp) + sizeof(offset); } }dx[id].jp.n[ij] = ndelx; dx[id].jp.x[ij] = xx; dx[id].score = delx; }else { col1[yy] = dely[yy]; ij = dx[id].ijmp; if (dx[id].jp.n[0] &&(!dna || (ndely[yy] >= MAXJMP && xx > dx[id].jp.x[ij]+MX) || mis >dx[id].score+DINS0)) { dx[id].ijmp ++; if (++ij >= MAXJMP) {writejmps(id); ij = dx[id].ijmp = 0; dx[id].offset = offset; offset +=sizeof(struct jmp) + sizeof(offset); } } dx[id].jp.n[ij] =−ndely[yy];dx[id].jp.x[ij] = xx; dx[id] .score = dely[yy]; } if (xx == len0 && yy <len1) { /* last col  */ if (endgaps) col1[yy] −= ins0+ins1*(len1−yy);if(col1[yy] > smax) { smax = col1[yy]; dmax = id; } } } if (endgaps &&xx < len0) col1[yy−1] −= ins0+ins1*(len0−xx); if (col1[yy−1] > smax) {smax = col1[yy−1]; dmax = id; } tmp = col0; col0 = col1; col1 = tmp; }(void) free((char *)ndely); (void) free((char *)dely); (void) free((char*)col0); (void) free((char *)col1); } /*  *  * print() -- only routinevisible outside this module  *  * static:  * getmat() -- trace back bestpath, count matches: print()  * pr_align() -- print alignment ofdescribed in array p[]: print()  * dumpblock() -- dump a block of lineswith numbers, stars: pr_align()  * nums() -- put out a number line:dumpblock()  * putline() -- put out a line (name, [num], seq, [num]):dumpblock()  * stars() - -put a line of stars: dumpblock()  *stripname() -- strip any path and prefix from a seqname  */ #include“nw.h” #define SPC  3 #define P_LINE 256 /* maximum output line */#define P_SPC  3 /* space between name or num and seq */ extern_day[26][26]; int olen; /* set output line length */ FILE *fr; /* outputfile */ print() print { int lx, ly, firstgap, lastgap;  /* overlap */ if((fx = fopen(ofile, “w”)) == 0) { fprintf(stderr, “%s: can't write%s\n”, prog, ofile); cleanup(1); } fprintf(fx, “<first sequence: %s(length = %d)\n”, namex[0], len0); fprintf(fx, “<second sequence: %s(length = %d)\n”, namex[1], len1); olen = 60; lx = len0; ly = len1;firstgap = lastgap = 0; if (dmax < len1 − 1) { /* leading gap in x */pp[0].spc = firstgap = len1 − dmax − 1; ly −= pp[0].spc; } else if(dmax > len1 − 1) { /* leading gap in y */ pp[1].spc = firstgap = dmax −(len1 − 1); lx −= pp[1].spc; } if (dmax0 < len0 − 1) { /* trailing gapin x */ lastgap = len0 − dmax0 −1; lx −= lastgap; } else if (dmax0 >len0 − 1) { /* trailing gap in y */ lastgap = dmax0 − (len0 − 1); ly −=lastgap; } getmat(lx, ly, firstgap, lastgap); pr_align(); } /*  * traceback the best path, count matches  */ static getmat(lx, ly, firstgap,lastgap) getmat int lx, ly; /* “core” (minus endgaps) */ int firstgap,lastgap; /* leading trailing overlap */ { int nm, i0, i1, siz0, siz1;char outx[32]; double pct; register n0, n1; register char *p0, *p1; /*get total matches, score  */ i0 = i1 = siz0 = siz1 = 0; p0 = seqx[0] +pp[1].spc; p1 = seqx[1] + pp[0].spc; n0 = pp[1].spc + 1; n1 =pp[0].spc + 1; nm = 0; while ( *p0 && *p1 ) { if (siz0) { p1++; n1++;siz0−−; } else if (siz1) { p0++; n0++; siz1−− } else { if(xbm[*p0−‘A’]&xbm[*p1−‘A’]) nm++; if (n0++ == pp[0].x[i0]) siz0 =pp[0].n[i0++]; if (nl++ == pp[1].x[i1]) siz1 = pp[1].n[il++]; p0++;p1++; } } /* pct homology:  * if penalizing endgaps, base is the shorterseq  * else, knock off overhangs and take shorter core  */ if (endgaps)lx = (len0 < len1)? len0 : len1; else lx = (lx < ly)? lx : ly; pct =100.*(double)nm/(double)lx; fprintf(fx, “\n”); fprintf(fx, “<%d match%sin an overlap of %d: %.2f percent similarity\n”, nm, (nm == 1)? “” :“es”, lx, pct); fprintf(fx, “, gaps in first sequence: %d”, gapx);...getmat if (gapx) { (void) sprintf(outx, “(%d %s%s)”, ngapx, (dna)?“base”: “residue”, (ngapx == 1)? “”:“s”); fprintf(fr, “% s”, outx);fprintf(fx, “, gaps in second sequence: %d”, gapy); if (gapy) { (void)sprintf(outx, “(%d %s%s)”, ngapy, (dna)? “base”:“residue”, (ngapy == 1)?“”:“s”); fprintf(fx, “%s”, outx); } if (dna) fprintf(fx, “\n<score: %d(match = %d, mismatch = %d, gap penalty = %d + %d per base)\n”, smax,DMAT, DMIS, DINS0, DINS1); else fprintf(fx, “\n<score: %d (Dayhoff PAM250 matrix, gap penalty = %d + %d per residue)\n”, smax, PINS0, PINS1);if (endgaps) fprintf(fx, “<endgaps penalized. left endgap: %d %s%s,right endgap: %d %s%s\n”, firstgap, (dna)? “base”: “residue”, (firstgap== 1)? “” : “s”, lastgap, (dna)? “base”: “residue”, (lastgap == 1)? “” :“s”); else fprintf(fx, “<endgaps not penalized\n”); } static nm; /*matches in core -- for checking */ static lmax; /* lengths of strippedfile names */ static ij[2]; /* jmp index for a path */ static nc[2]; /*number at start of current line */ static ni[2]; /* current elem number-- for gapping */ static siz[2]; static char *ps[2]; /* ptr to currentelement */ static char *po[2]; /* ptr to next output char slot */ staticchar out[2][P_LINE]; /* output line */ static char star[P_LINE]; /* setby stars() */ /*  * print alignment of described in struct path pp[]  */static pr_align() pr_align { int nn; /* char count */ int more; registeri; for (i = 0, lmax = 0; i < 2++) { nn = stripname(namex[i]); if (nn >lmax) lmax = nn; nc[i] = 1; ni[i] = 1; siz[i] = ij[i] = 0; ps[i] =seqx[i]; po[i] = out[i]; } for (nn = nm = 0, more = 1; more;) {...pr_align for (i = more = 0; i < 2; i++) { /*  * do we have more ofthis sequence?  */ if (!*ps[i]) continue; more ++; if (pp[i].spc) { /*leading space */ *po[i]++ = ‘ ’; pp[i] .spc−−; } else if (siz[i]) { /*in a gap */ *po[i]++ = ‘−’; siz[i]−−; } else { /* we're putting a seqelement */ *po[i] = *ps[i]; if (islower(*ps[i])) *ps[i] =toupper(*ps[i]); po[i]++; ps[i]++; /*  * are we at next gap for thisseq?  */ if (ni[i] == pp[i].x[ij[i]]) { /*  * we need to merge all gaps * at this location  */ siz[i] == pp[i].n[ij[i]++]; while (ni[i] ==pp[i].x[ij[i]]) siz[i] += pp[i].n[ij[i] ++]; } ni[i] ++; } } if (++nn ==olen || !more && nn) { dumpblock(); for (i = 0; i < 2; i++) po[i] =out[i]; nn = 0; } } } /*  * dump a block of lines, including numbers,stars: pr_align()  */ static dumpblock() dumpblock { register i; for(i =0; i < 2; i++) *po[i]−− = ‘\0’; ...dumpblock (void) putc(‘\n’, fx); for(i = 0; i < 2; i++) { if (*out [i] && (*out[i] != ‘ ’ || *(po[i]) != ‘’)) { if (i == 0) nums(i); if (i == 0 && *out[1]) stars(); putline(i);if (i == 0 && *out[1]) fprintf(fx, star); if (i == 1) nums(i); } } }/* * put out a number line: dumpblock()  */ static nums(ix) numsint  ix; /* index in out[] holding seq line */ { char nline[P_LINE];register i, j; register char *pn, *px, *py; for(pn = nline, i = 0; i <lmax+P_SPC; i++, pn++) *pn = ‘ ’; for (i = nc[ix], py = out[ix]; *py;py++, pn++) { if (*py == ‘ ’ || *py == ‘−’); *pn = ‘ ’; else { if (i%10== 0 || (i == 1 && nc[ix] != 1)) { j = (i < 0)? −i ; i; for (px = pn; j;j/= 10, px−−) *px = j%10 + ‘0’; if (i < 0) *px = ‘−’; } else *pn = ‘ ’;i++; } } *pn = ‘\0’; nc[ix] = i; for (pn = nline; *pn; pn++) (void)putc(*pn, fx); (void) putc(‘\n’, fx); } /*  * put out a line (name,[num], seq. [num]): dumpblock()  */ static putline(ix) putline int   ix;{ ...putline int i; register char *px; for (px = namex[ix], i = 0; *px&& *px != ‘:’; px++, i++) (void) putc(*px, fx); for (;i < lmax + P_SPC;i++) (void) putc(‘ ’, fx); /* these count from 1:  * ni[] is currentelement (from 1)  * nc[] is number at start of current line  */ for (px= out[ix]; *px; px++) (void) putc(*px&0x7F, fx); (void) putc(‘\n’, fx);} /*  * put a line of stars (seqs always in out[0], out[1]): dumpblock() */ static stars() stars { int i; register char *p0, *p1, cx, *px; if(!*out[0] || (*out[0] == ‘ ’ && *(p0[0]) == ‘ ’) || !*out[1] || (*out[1] == ‘ ’ && *(po[1]) == ‘ ’)) return; px = star; for (i = lmax +P_SPC; i; i−−) *px++ = ‘ ’; for (p0 = out[0], p1 = out[1]; *p0 && *p1;p0++, p1++) { if (isalpha(*p0) && isalpha(*p1)) { if(xbm[*p0−‘A’]&xbm[*p1−‘A’]) { cx = ‘*’; nm++; } else if (!dna &&_day[*p0− ‘A’][*p1−‘A’] > 0) cx = ‘.’; else cx = ‘ ’; } else cx = ‘ ’;*px++ = cx; } *px++ = ‘\n’; *px = ‘\0’; } /*  * strip path or prefixfrom pn, return len: pr_align()  */ static stripname(pn) stripname char*pn; /* file name (may be path) */ { register char *px, *py; py = 0; for(px = pn; *px; px++) if (*px == ‘/’) py = px + 1; if (py) (void)strcpy(pn, py); return(strlen(pn)); } /*  * cleanup() -- cleanup any tmpfile  * getseq() -- read in seq, set dna, len, maxlen  * g_calloc() --calloc() with error checkin  * readjmps() -- get the good jmps, from tmpfile if necessary  * writejmps() -- write a filled array of jmps to atmp file: nw()  */ #include “nw.h” #include <sys/file.h> char *jname =“/tmp/homgXXXXXX”; /* tmp file for jmps */ FILE *fj; int cleanup(); /*cleanup tmp file */ long lseek(); /*  * remove any tmp file if we blow */ cleanup(i) cleanup int i; { if (fj) (void) unlink(jname); exit(i); }/*  * read, return ptr to seq, set dna, len, maxlen  * skip linesstarting with ‘;’, ‘<’, or ‘>’  * seq in upper or lower case  */ char *getseq(file, len) getseq char *file; /* file name */ int *len; /* seqlen */ { char line[1024], *pseq; register char *px, *py; int natgc,tlen; FILE *fp; if ((fp = fopen(file, “r”)) == 0) { fprintf(stderr, “%s:can't read %s\n”, prog, file); exit(1); } tlen = natgc = 0; while(fgets(line, 1024, fp)) { if (*line == ‘;’ || *line == ‘<’ || *line ==‘>’) continue; for (px = line; *px != ‘\n’; px++) if (isupper(*px) ||islower(*px)) tlen++; } if ((pseq = malloc((unsigned)(tlen+6))) == 0) {fprintf(stderr, “%s: malloc() failed to get %d bytes for %s\n”, prog,tlen+6, file); exit(1); } pseq[0] = pseq[1] = pseq[2] = pseq[3] = ‘\0’;...getseq py = pseq + 4; *len = tlen; rewind(fp); while (fgets(line,1024, fp)) { if (*line == ‘;’ || *line == ‘<’ || *line == ‘>’) continue;for (px = line; *px != ‘\n’; px++) { if (isupper(*px)) *py++ = *px; elseif (islower(*px)) *py++ = toupper(*px); if (index(“ATGCU”, *(py−1)))natgc++; } } *py++ = ‘\0’; *py = ‘\0’; (void) fclose(fp); dna = natgc >(tlen/3); return(pseq+4); } char * g_calloc(msg, nx, sz) g_calloc char*msg; /* program, calling routine */ int nx, sz; /* number and size ofelements */ { char *px, *calloc(); if ((px = calloc((unsigned)nx,(unsigned)sz)) == 0) { if (*msg) { fprintf(stderr, “%s: g_calloc()failed %s (n= %d, sz= %d)\n”, prog, msg, nx, sz); exit(1); } }return(px); } /*  * get final jmps from dx[] or tmp file, set pp[],reset dmax: main()  */ readjmps() readjmps { int fd = −1; int siz, i0,i1; register i, j, xx; if (fj) { (void) fclose(fj); if ((fd =open(jname, O_RDONLY, 0)) < 0) { fprintf(stderr, “%s: can't open()%s\n”, prog, jname); cleanup(1); } } for (i = i0 = i1 = 0, dmax0 = dmax,xx = len0; ;i++) { while (1) { for (j = dx[dmax].ijmp; j >= 0 &&dx[dmax].jp.x[j] >= xx; j−−) ...readjmps if (j < 0 && dx[dmax].offset &&fj) { (void) lseek(fd, dx[dmax].offset, 0); (void) read(fd, (char*)&dx[dmax].jp, sizeof(struct jmp)); (void) read(fd, (char*)&dx[dmax].offset, sizeof(dx[dmax].offset)); dx[dmax].ijmp = MAXJMP−1;} else break; } if (i >= JMPS) { fprintf(stderr, “%s: too many gaps inalignment\n”, prog); cleanup(1); } if (j >= 0) { siz = dx[dmax].jp.n[j];xx = dx[dmax].jp.x[j]; dmax += siz; if (siz < 0) { /* gap in second seq*/ pp[1].n[il] = −siz; xx += siz; /* id = xx − yy + len1 − 1  */pp[1].x[il] = xx − dmax + len1 − 1; gapy++; ngapy −= siz; /* ignoreMAXGAP when doing endgaps */ siz = (−siz < MAXGAP || endgaps)? −siz :MAXGAP; il++; } else if (siz > 0) { /* gap in first seq */ pp[0] .n[i0]= siz; pp[0] .x[i0] = xx; gapx++; ngapx += siz; /* ignore MAXGAP whendoing endgaps */ siz = (siz < MAXGAP || endgaps)? siz : MAXGAP; i0++; }} else break; } /* reverse the order of jmps  */ for (j = 0, i0−−; j <i0; j++, i0−−) { i = pp[0].n[j]; pp[0].n[j] = pp[0].n[i0]; pp[0].n[i0] =i; i = pp[0].x[j]; pp[0].x[j] = pp[0].x[i0]; pp[0].x[i0] = i; } for (j =0, i1−−;j < i1; j++, i1−−) { i = pp[1].n[j]; pp[1].n[j] = pp[1].n[i1];pp[1].n[i1] = i; i = pp[1].x[j]; pp[1].x[j] = pp[1].x[i1]; pp[1].x[i1] =i; } if (fd >= 0) (void) close(fd); if (fj) { (void) unlink(jname); fj =0; offset = 0; } } /*  * write a filled jmp struct offset of the prevone (if any): nw()  */ writejmps(ix) writejmps int ix; { char *mktemp();if (!fj) { if (mktemp(jname) < 0) { fprintf(stderr, “%s: can't mktemp()%s\n”, prog, jname); cleanup(1); } if ((fj = fopen(jname, “w”) == 0) {fprintf(stderr, “%s: can't write %s\n”, prog, jname); exit(1); } }(void) fwrite((char *)&dx[ix].jp, sizeof( struct jmp), 1, fj); (void)fwrite((char *)&dx[ix].offset, sizeof(dx[ix].offset), 1, fj); }

[2968] TABLE 2 PRO XXXXXXXXXXXXXXX (Length = 15 amino acids) ComparisonXXXXXYYYYYYY (Length = 12 amino acids) Protein

[2969] TABLE 3 PRO XXXXXXXXXX (Length = 10 amino acids) ComparisonXXXXXYYYYYYZZYZ (Length = 15 amino acids) Protein

[2970] TABLE 4 PRO-DNA NNNNNNNNNNNNNN (Length = 14 nucleotides)Comparison NNNNNNLLLLLLLLLL (Length = 16 nucleotides) DNA

[2971] TABLE 5 PRO-DNA NNNNNNNNNNNN (Length = 12 nucleotides) ComparisonNNNNLLLVV (Length = 9 nucleotides) DNA

[2972] II. Compositions and Methods of the Invention

[2973] A. Full-length PRO Polypeptides

[2974] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO polypeptides. In particular, cDNAs encoding variousPRO polypeptides have been identified and isolated, as disclosed infurther detail in the Examples below. It is noted that proteins producedin separate expression rounds may be given different PRO numbers but theUNQ number is unique for any given DNA and the encoded protein, and willnot be changed. However, for sake of simplicity, in the presentspecification the protein encoded by the full length native nucleic acidmolecules disclosed herein as well as all further native homologues andvariants included in the foregoing definition of PRO, will be referredto as “PRO/number”, regardless of their origin or mode of preparation.

[2975] As disclosed in the Examples below, various cDNA clones have beendeposited with the ATCC. The actual nucleotide sequences of those clonescan readily be determined by the skilled artisan by sequencing of thedeposited clone using routine methods in the art. The predicted aminoacid sequence can be determined from the nucleotide sequence usingroutine skill. For the PRO polypeptides and encoding nucleic acidsdescribed herein, Applicants have identified what is believed to be thereading frame best identifiable with the sequence information availableat the time.

[2976] 1. Full-length PRO281 Polypeptides

[2977] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO281 (UNQ244). In particular, cDNA encoding a PRO281polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[2978] Using the WU-BLAST-2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO281 (shown in FIG. 2and SEQ ID NO:2) has certain amino acid sequence identity with the ratTEGT protein. Accordingly, it is presently believed that PRO281disclosed in the present application is a newly identified TEGT homologand may possess activity typical of that protein.

[2979] 2. Full-length PRO276 Polypeptides

[2980] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO276 (UNQ243). In particular, cDNA encoding a PRO276polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[2981] As far as is known, the DNA16435-1208 sequence encodes a novelfactor designated herein as PRO276; using WU-BLAST-2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed. The sequence identity identifications which werefound are listed below in the examples.

[2982] 3. Full-length PRO189 Polypeptides

[2983] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO189. In particular, Applicants have identified andisolated cDNA encoding a PRO189 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA21624-1391 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, no significant sequenceidentities to any known proteins were revealed.

[2984] 4. Full-length PRO190 Polypeptides

[2985] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO190. In particular, Applicants have identified andisolated cDNA encoding a PRO190 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO190-encoding clone was isolatedfrom a human retina library. To Applicants present knowledge, theDNA23334-1392 nucleotide sequence encodes a novel multiple transmembranespanning protein; using BLAST and FastA sequence alignment computerprograms, there is some sequence identity with CMP-sialic acid andUDP-galactose transporters, indicating that PRO190 may be related totransporter or that PRO190 may be a novel transporter.

[2986] 5. Full-length PRO341 Polypeptides

[2987] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO341 (UNQ300). In particular, cDNA encoding a PRO341polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[2988] The DNA26288-1239 clone was isolated from a human placentalibrary. As far as is known, the DNA26288-1239 sequence encodes a novelfactor designated herein as PRO341; using the WU-BLAST-2 sequencealignment computer program, no significant sequence identities to anyknown proteins were revealed.

[2989] 6. Full-length PRO180 Polypeptides

[2990] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO180 (UNQ154). In particular, cDNA encoding a PRO180polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[2991] The DNA26843-1389 clone was isolated from a human placentalibrary using oligos formed from DNA12922 isolated from an amylasescreen. As far as is known, the DNA26843-1389 sequence encodes a novelfactor designated herein as PRO180.

[2992] 7. Full-length PRO194 Polypeptides

[2993] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO194. In particular, Applicants have identified andisolated cDNA encoding a PRO194 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO194-encoding clone was isolatedfrom a human fetal lung library. To Applicants present knowledge, theDNA26844-1394 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, no significant sequenceidentities to any known proteins were revealed.

[2994] 8. Full-length PRO203 Polypeptides

[2995] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO203. In particular, Applicants have identified andisolated cDNA encoding a PRO203 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO203 polypeptide hassequence identity with GST ATPase. Accordingly, it is presently believedthat PRO203 polypeptide disclosed in the present application is a newlyidentified member of the ATPase family and possesses activity typical ofthe GST ATPase.

[2996] 9. Full-length PRO290 Polypeptides

[2997] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO290. In particular, cDNA encoding a PRO290 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[2998] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST2 sequence alignment analysis of the full-lengthsequence shown in FIG. 23 (SEQ ID NO:33), revealed sequence identitiesbetween the PRO290 amino acid sequence and the following Dayhoffsequences:P_R99800, CC4H_HUMAN, YCS2_YEAST, CEF35G12_(—)13, HSFAN_(—)1,MMU52461_(—)1, MMU70015_(—)1, HSU67615_(—)1, CET01H10_(—)8 andCELT28F2_(—)6.

[2999] It is currently believed that PRO290 is an intracellular proteinrelated to one or more of the above proteins.

[3000] 10. Full-length PRO874 Polypeptides

[3001] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO874. In particular, Applicants have identified andisolated cDNA encoding a PRO874 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO874-encoding clone was isolatedfrom a human fetal lung library. To Applicants present knowledge, theDNA40621-1440 nucleotide sequence encodes a novel factor. Although,using BLAST and FastA sequence alignment computer programs, somesequence identity with known proteins was revealed.

[3002] 11. Full-length PRO710 Polypeptides

[3003] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO710. In particular, Applicants have identified andisolated cDNA encoding a PRO710 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO710 polypeptide hassignificant similarity to the CDC45 protein. Accordingly, it ispresently believed that PRO710 polypeptide disclosed in the presentapplication is a newly identified CDC45 homolog.

[3004] 12. Full-length PRO1151 Polypeptides

[3005] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1151. In particular, cDNA encoding a PRO1151polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3006] Using the WU-BLAST-2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1151 (shown in FIG. 30and SEQ ID NO:47) has certain amino acid sequence identity with thehuman 30 kD adipocyte complement-related precursor protein (ACR3_HUMAN).Accordingly, it is presently believed that PRO1151 disclosed in thepresent application is a newly identified member of the complementprotein family and may possess activity typical of that family.

[3007] 13. Full-length PRO1282 Polypeptides

[3008] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1282. In particular, cDNA encoding a PRO1282polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3009] As far as is known, the DNA45495-1550 sequence encodes a novelfactor designated herein as PRO1282. Using WU-BLAST-2 sequence alignmentcomputer programs, some sequence identities between PRO1282 and otherleucine rich repeat proteins were revealed, as discussed in the examplesbelow, indicating that a novel member of the leucine rich repeatsuperfamily has been identified.

[3010] 14. Full-length PRO358 Polypeptides

[3011] The present invention further provides newly identified andisolated nucleotide sequences encoding a polypeptide referred to in thepresent application as PRO358. In particular, Applicants have identifiedand isolated cDNA encoding a novel human Toll polypeptide (PRO358), asdisclosed in further detail in the Examples below. Using BLAST and FastAsequence alignment computer programs, Applicants found that the codingsequence of PRO358 shows significant homology to DNA sequencesHSU88540_(—)1, HSU88878_(—)1, HSU88879_(—)1, HSU88880_(—)1,HS88881_(—)1, and HSU79260_(—)1 in the GenBank database. With theexception of HSU79260_(—)1, the noted proteins have been identified ashuman toll-like receptors.

[3012] Accordingly, it is presently believed that the PRO358 proteinsdisclosed in the present application are newly identified humanhomologues of the Drosophila protein Toll, and are likely to play animportant role in adaptive immunity. More specifically, PRO358 may beinvolved in inflammation, septic shock, and response to pathogens, andplay possible roles in diverse medical conditions that are aggravated byimmune response, such as, for example, diabetes, ALS, cancer, rheumatoidarthritis, and ulcers. The role of PRO385 as pathogen patternrecognition receptors, sensing the presence of conserved molecularstructures present on microbes, is further supported by the datadisclosed in the present application, showing that a known humanToll-like receptor, TLR2 is a direct mediator of LPS signaling.

[3013] 15. Full-length PRO1310 Polypeptides

[3014] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1310. In particular, cDNA encoding a PRO1310polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3015] Using WU-BLAST-2 sequence alignment computer programs, it hasbeen found that a full-length native sequence PRO1310 (shown in FIG. 36and SEQ ID NO:62) has certain amino acid sequence identity withcarboxypeptidase X2. Accordingly, it is presently believed that PRO1310disclosed in the present application is a newly identified member of thecarboxypeptidase family and may possess carboxyl end amino acid removalactivity.

[3016] 16. Full-length PRO698 Polypeptides

[3017] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO698. In particular, Applicants have identified andisolated cDNA encoding a PRO698 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO698 polypeptide hassignificant similarity to the olfactomedin protein. Accordingly, it ispresently believed that PRO698 polypeptide disclosed in the presentapplication may be a newly identified olfactomedin homolog.

[3018] 17. Full-length PRO732 Polypeptides

[3019] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO732. In particular, Applicants have identified andisolated cDNA encoding a PRO732 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO732 polypeptide hassignificant similarity to the human placental Diff33 protein.Accordingly, it is presently believed that PRO732 polypeptide disclosedin the present application is a newly identified Diff33 homolog.

[3020] 18. Full-length PRO1120 Polypeptides

[3021] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1120. In particular, cDNA encoding a PRO1120polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3022] Using WU-BLAST-2 sequence alignment computer programs, it hasbeen found that a full-length native sequence PRO1120 (shown in FIG. 47and SEQ ID NO:84) has certain amino acid sequence identity with theknown sulfatase proteins designated CELK09C4_(—)1, and GL6S_HUMAN,respectively, in the Dayhoff database (version 35.45 SwissProt 35).Accordingly, it is presently believed that PRO1120 disclosed in thepresent application is a newly identified member of the sulfatase familyand may possess activity typical of sulfatases.

[3023] 19. Full-length PRO537 Polypeptides

[3024] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO537. In particular, cDNA encoding a PRO537 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below. The DNA49141-1431 clone was isolated from a humanplacenta library using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA49141-1431 clone doesencode a secreted factor. As far as is known, the DNA49141-1431 sequenceencodes a novel factor designated herein as PRO537; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3025] 20. Full-length PRO536 Polypeptides

[3026] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO536. In particular, cDNA encoding a PRO536 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3027] The DNA49142-1430 clone was isolated from a human infant brainlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA49142-1430 clone doesencode a secreted factor. As far as is known, the DNA49142-1430 sequenceencodes a novel factor designated herein as PRO536; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3028] 21. Full-length PRO535 Polypeptides

[3029] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO535. In particular, cDNA encoding a PRO535 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3030] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO535 (shown in FIG. 53and SEQ ID NO:99) has amino acid sequence identity with a putativepeptidyl-prolyl isomerase protein. Accordingly, it is presently believedthat PRO535 disclosed in the present application is a newly identifiedmember of the isomerase protein family and may possess activity typicalof those proteins.

[3031] 22. Full-length PRO718 Polypeptides

[3032] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO718. In particular, Applicants have identified andisolated cDNA encoding a PRO718 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO718-encoding clone was isolatedfrom a human fetal lung library. To Applicants present knowledge, theDNA49647-1398 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, no significant sequenceidentities to any known proteins were revealed.

[3033] 23. Full-length PRO872 Polypeptides

[3034] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO872. In particular, Applicants have identified andisolated cDNA encoding a PRO872 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO872 polypeptide hassequence identity with dehydrogenases. Accordingly, it is presentlybelieved that PRO872 polypeptide disclosed in the present application isa newly identified member of the dehydrogenase family and possessesdehydrogenase activity.

[3035] 24. Full-length PRO1063 Polypeptides

[3036] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1063. In particular, Applicants have identified andisolated cDNA encoding a PRO1063 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1063 polypeptide hassignificant similarity to the human type IV collagenase protein.Accordingly, it is presently believed that PRO1063 polypeptide disclosedin the present application is a newly identified collagenase homolog.

[3037] 25. Full-length PRO619 Polypeptides

[3038] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO619. In particular, cDNA encoding a PRO619 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3039] Using WU-BLAST-2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO619 (shown in FIG. 68 andSEQ ID NO:117) has certain amino acid sequence identity with VpreB3.Accordingly, it is presently believed that PRO619 disclosed in thepresent application is a newly identified member of the IgG superfamilyand may possess activity related to the assembly and/or components ofthe surrogate light chain associated with developing B cells.

[3040] 26. Full-length PRO943 Polypeptides

[3041] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO943. In particular, cDNA encoding a PRO943 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3042] Using the WU-BLAST-2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO943 (shown in FIG. 70and SEQ ID NO:119) has amino acid sequence identity with the fibroblastgrowth factor receptor-4 protein. Accordingly, it is presently believedthat PRO943 disclosed in the present application is a newly identifiedmember of the fibrobalst growth factor receptor family and may possessactivity typical of that family.

[3043] 27. Full-length PRO1188 Polypeptides

[3044] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1188. In particular, cDNA encoding a PRO1188polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3045] As discussed in more detail in Example 1 below, using WU-BLAST-2sequence alignment computer programs, it has been found that afull-length native sequence PRO1188 (shown in FIG. 72; SEQ ID NO:124)has certain amino acid sequence identity with nucleotidepyrophosphohydrolase (SSU83114_(—)1). Accordingly, it is presentlybelieved that PRO1188 disclosed in the present application is a newlyidentified member of the nucleotide pyrophosphohydrolase family and maypossess activity typical of that family of proteins.

[3046] 28. Full-length PRO1133 Polypeptides

[3047] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1133. In particular, cDNA encoding a PRO1133polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3048] Using WU-BLAST-2 sequence alignment computer programs, it hasbeen found that a full-length native sequence PRO1133 (shown in FIG. 74and SEQ ID NO:129) has certain amino acid sequence identity with netrin1a, Dayhoff accession AF002717_(—)1. Accordingly, it is presentlybelieved that PRO1133 disclosed in the present application shares atleast one related mechanism with netrin.

[3049] 29. Full-length PRO784 Polypeptides

[3050] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO784. In particular, cDNA, designated herein as“DNA53978-1443”, which encodes a PRO784 polypeptide, has been identifiedand isolated, as disclosed in further detail in the Examples below.

[3051] Using BLAST and FastA sequence alignment computer programs, ithas been found that a full-length native sequence PRO784 (shown in FIG.76 and SEQ ID NO:135) has certain amino acid sequence identity withsec22 homologs. Accordingly, it is presently believed that PRO784disclosed in the present application is a newly identified member of thesec22 family and may possess vesicle trafficking activities typical ofthe sec22 family.

[3052] 30. Full-length PRO783 Polypeptides

[3053] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO783. In particular, Applicants have identified andisolated cDNA encoding a PRO783 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO783-encoding clone was isolatedfrom a human fetal kidney library. To Applicants present knowledge, theDNA53996-1442nucleotide sequence encodes a novel factor. However, usingBLAST and FastA sequence alignment computer programs, some sequenceidentity to known proteins was found.

[3054] 31. Full-length PRO820 Polypeptides

[3055] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO820. In particular, Applicants have identified andisolated cDNA encoding a PRO820 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that various portions of the PRO820polypeptide have sequence identity with the low affinity immunoglobulingamma Fc receptor, the IgE high affinity Fc receptor and the highaffinity immunoglobulin epsilon receptor. Accordingly, it is presentlybelieved that PRO820 polypeptide disclosed in the present application isa newly identified member of the Fc receptor family.

[3056] 32. Full-length PRO1080 Polypeptides

[3057] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1080. In particular, Applicants have identified andisolated cDNA encoding a PRO1080 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Dayhoff database (version 35.45 SwissProt 35),Applicants found that the PRO1080 polypeptide has sequence identity witha 39.9 kd protein designated as “YRY1_CAEEL”, a DnaJ homolog designated“AF027149_(—)5”, a DnaJ homolog 2 designated “RNU95727_(—)1”, andDna3/Cpr3 designated “AF011793_(—)1”. Accordingly, these resultsindicate that the PRO1080 polypeptide disclosed in the presentapplication may be a newly identified member of the DnaJ-like proteinfamily and therefore may be involved in protein biogenesis.

[3058] 33. Full-length PRO1079 Polypeptides

[3059] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1079. In particular, cDNA encoding a PRO1079polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3060] As far as is known, the DNA56050-1455 sequence encodes a novelfactor designated herein as PRO1079. Although, using WU-BLAST2 sequencealignment computer programs, some sequence identities to known proteinswas revealed.

[3061] 34. Full-length PRO793 Polypeptides

[3062] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO793. In particular, cDNA encoding a PRO793 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3063] The DNA56110-1437 clone was isolated from a human skin tumorlibrary. As far as is known, the DNA56110-1437 sequence encodes a novelfactor designated herein as PRO793; using the WU-BLAST-2 sequencealignment computer program, no significant sequence identities to anyknown proteins were revealed.

[3064] 35. Full-length PRO1016 Polypeptides

[3065] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1016. In particular, Applicants have identified andisolated cDNA encoding a PRO1016 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that various portions of the PRO1016polypeptide have sequence identity with acyltransferases. Accordingly,it is presently believed that PRO1016 polypeptide disclosed in thepresent application is a newly identified member of the acyltransferasefamily and possesses acyltalation capabilities typical of this family.

[3066] 36. Full-length PRO1013 Polypeptides

[3067] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1013. In particular, Applicants have identified cDNAencoding a PRO1013 polypeptide, as disclosed in further detail in theExamples below. The PRO1013-encoding clone came from a human breasttumor tissue library. Thus, the PRO1013-encoding clone may encode asecreted factor related to cancer. To Applicants present knowledge, theDNA56410-1414 nucleotide sequence encodes a novel factor. Using BLASTand FastA sequence alignment computer programs, some sequence identitywith KIAA0157 and P120 was revealed. PRO1013 has at least one region incommon with growth factor and cytokine receptors.

[3068] 37. Full-length PRO937 Polypeptides

[3069] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO937. In particular, Applicants have identified andisolated cDNA encoding a PRO937 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO937 polypeptide hassignificant sequence identity with members of the glypican family ofproteins. Accordingly, it is presently believed that PRO937 polypeptidedisclosed in the present application is a newly identified member of theglypican family possesses properties typical of the glypican family.

[3070] 38. Full-length PRO842 Polypeptides

[3071] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO842. In particular, cDNA encoding a PRO842 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3072] As far as is known, the DNA56855-1447 sequence encodes a novelsecreted factor designated herein as PRO842. However, using WU-BLAST2sequence alignment computer programs, some sequence identity to anyknown proteins were revealed.

[3073] 39. Full-length PRO839 Polypeptides

[3074] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO839. In particular, cDNA encoding a PRO839 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3075] As far as is known, the DNA56859-1445 sequence encodes a novelfactor designated herein as PRO839. However, using WU-BLAST-2 sequencealignment computer programs, some sequence identities to known proteinswas revealed.

[3076] 40. Full-length PRO1180 Polypeptides

[3077] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1180. In particular, Applicants have identified andisolated cDNA encoding a PRO1180 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1180 polypeptide hassignificant similarity to methyltransferase enzymes. Accordingly, it ispresently believed that PRO1180 polypeptide disclosed in the presentapplication is a newly identified member of the methyltransferase familyand possesses activity typical of that family.

[3078] 41. Full-length PRO1134 Polypeptides

[3079] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1134. In particular, cDNA encoding a PRO1134polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3080] The DNA56865-1491 clone was isolated from a human fetal liverspleen library using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA56865-1491 clone doesencode a secreted factor. As far as is known, the DNA56865-1491 sequenceencodes a novel factor designated herein as PRO1134; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3081] 42. Full-length PRO830 Polypeptides

[3082] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO830. In particular, cDNA encoding a PRO830 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3083] The DNA56866-1342 clone was isolated from a human fetalliver/spleen library using a trapping technique which selects fornucleotide sequences encoding secreted proteins. Thus, the DNA56866-1342clone does encode a secreted factor. As far as is known, theDNA56866-1342 sequence encodes a novel factor designated herein asPRO830; using the WU-BLAST-2 sequence alignment computer program, nosignificant sequence identities to any known proteins were revealed.

[3084] 43. Full-length PRO1115 Polypeptides

[3085] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1115. In particular, cDNA encoding a PRO1115polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3086] As far as is known, the DNA56868-1478 sequence encodes a noveltransmembrane protein designated herein as PRO1115. Although, usingWU-BLAST-2 sequence alignment computer programs, some sequenceidentities to known proteins were revealed.

[3087] 44. Full-length PRO1277 Polypeptides

[3088] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1277. In particular, cDNA encoding a PRO1277polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3089] Using WU-BLAST-2 sequence alignment computer programs, it hasbeen found that a full-length native sequence PRO1277 (shown in FIG. 113and SEQ ID NO:179) has certain amino acid sequence identity withCoch-5B2 protein (designated “AF012252_(—)1, in the Dayhoff database).Accordingly, it is presently believed that PRO1277 disclosed in thepresent application is a newly identified member of the Coch-5B2 proteinfamily and may possess the same activities and properties as Coch-5B2.

[3090] 45. Full-length PRO1135 Polypeptides

[3091] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1135. In particular, Applicants have identified andisolated cDNA encoding a PRO1135 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1135 polypeptide hassignificant similarity to the alpha 1,2-mannosidase protein.Accordingly, it is presently believed that PRO1135 polypeptide disclosedin the present application is a newly identified member of themannosidase enzyme family and possesses activity typical of that familyof proteins.

[3092] 46. Full-length PRO1114 Polypeptides

[3093] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1114 interferon receptor. In particular, cDNA encodinga PRO1114 interferon receptor polypeptide has been identified andisolated, as disclosed in further detail in the Examples below.

[3094] Using the WU-BLAST-2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1114 interferonreceptor polypeptide (shown in FIG. 117 and SEQ ID NO:183) has sequenceidentity with the other known interferon receptors. Accordingly, it ispresently believed that PRO1114 interferon receptor possesses activitytypical of other interferon receptors.

[3095] 47. Full-length PRO828 Polypeptides

[3096] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO828. In particular, Applicants have identified andisolated cDNA encoding a PRO828 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO828 polypeptide hassequence identity with glutathione peroxidases. Accordingly, it ispresently believed that PRO828 polypeptide disclosed in the presentapplication is a newly identified member of the glutathione peroxidasefamily and possesses peroxidase activity and other properties typical ofglutathione peroxidases.

[3097] 48. Full-length PRO1009 Polypeptides

[3098] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1009. In particular, cDNA encoding a PRO1009polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3099] Using WU-BLAST-2 sequence alignment computer programs, it hasbeen found that a full-length native sequence PRO1009 (shown in FIG. 122and SEQ ID NO:194) has certain amino acid sequence identity withlong-chain acyl-CoA synthetase homolog designated “F69893 ”.Accordingly, it is presently believed that PRO1009 disclosed in thepresent application is a newly identified member of the long-chainacyl-CoA synthetase family and may possess activity related to thisfamily.

[3100] 49. Full-length PRO1007 Polypeptides

[3101] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1007. In particular, Applicants have identified andisolated cDNA encoding a PRO1007 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that various portions of the PRO1007polypeptide have sequence identity with MAGPIAP. Accordingly, it ispresently believed that PRO1007 polypeptide disclosed in the presentapplication is a newly identified member of the MAGPIAP family and isassociated with metastasis and/or cell signaling and/or cellreplication.

[3102] 50. Full-length PRO1056 Polypeptides

[3103] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1056. In particular, cDNA encoding a PRO1056polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3104] Using the WU-BLAST-2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1056 (shown in FIG. 127and SEQ ID NO:199) has amino acid sequence identity with a chloridechannel protein. Accordingly, it is presently believed that PRO1056disclosed in the present application is a newly identified chloridechannel protein homolog.

[3105] 51. Full-length PRO826 Polypeptides

[3106] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO826. In particular, cDNA encoding a PRO826 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3107] The DNA57694-1341 clone was isolated from a human fetal heartlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA57694-1341 clone doesencode a secreted factor. As far as is known, the DNA57694-1341 sequenceencodes a novel factor designated herein as PRO826; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3108] 52. Full-length PRO819 Polypeptides

[3109] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO819. In particular, cDNA encoding a PRO819 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3110] The DNA57695-1340 clone was isolated from a human fetal liverspleen library using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA57695-1340 clone doesencode a secreted factor. As far as is known, the DNA57695-1340 sequenceencodes a novel factor designated herein as PRO819; using the WU-BLAST-2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3111] 53. Full-length PRO1006 Polypeptides

[3112] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1006. In particular, Applicants have identified andisolated cDNA encoding a PRO1006 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO1006-encoding clone was isolatedfrom a human uterus library. To Applicants present knowledge, theDNA57699-1412 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, some sequence identitywith a putative tyrosine protein kinase was revealed.

[3113] 54. Full-length PRO1112 Polypeptides

[3114] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1112. In particular, Applicants have identified cDNAencoding a PRO1112 polypeptide, as disclosed in further detail inExample 1 below. To Applicants present knowledge, the DNA57702-1476nucleotide sequence encodes a novel factor, although using BLAST andFastA sequence alignment computer programs some sequence identity withother known proteins was found.

[3115] 55. Full-length PRO1074 Polypeptides

[3116] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1074. In particular, Applicants have identified andisolated cDNA encoding a PRO1074 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1074 polypeptide hassequence identity with galactosyltransferase. Accordingly, it ispresently believed that PRO1074 polypeptide disclosed in the presentapplication is a newly identified member of the galactosyltransferasefamily and possesses galactosyltransferase activity.

[3117] 56. Full-length PRO1005 Polypeptides

[3118] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1005. In particular, cDNA encoding a PRO1005polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3119] As far as is known, the DNA57708-1411 sequence encodes a novelfactor designated herein as PRO1005. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities with knownproteins was revealed.

[3120] 57. Full-length PRO1073 Polypeptides

[3121] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1073. In particular, cDNA encoding a PRO1073polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3122] As far as is known, the DNA57710 sequence encodes a novelsecreted factor designated herein as PRO1073. However, using WU-BLAST2sequence alignment computer programs, some sequence identities to knownproteins were revealed.

[3123] 58. Full-length PRO1152 Polypeptides

[3124] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1152. In particular, cDNA encoding a PRO1152polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3125] The DNA57711-1501 clone was isolated from a human infant brainlibrary. As far as is known, the DNA57711-1501 sequence encodes a novelfactor designated herein as PRO1152; using the WU-BLAST-2 sequencealignment computer program, no significant sequence identities to anyknown proteins were revealed.

[3126] 59. Full-length PRO1136 Polypeptides

[3127] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1136. In particular, cDNA encoding a PRO1136polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3128] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1136 (shown in FIG. 147and SEQ ID NO:219) has amino acid sequence identity with PDZdomain-containing proteins. Accordingly, it is presently believed thatPRO1136 disclosed in the present application is a newly identifiedmember of the PDZ domain-containing protein family and may possessactivity typical of that family.

[3129] 60. Full-length PRO813 Polypeptides

[3130] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO813. In particular, Applicants have identified andisolated cDNA encoding a PRO813 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO813 polypeptide hassignificant similarity to the pulmonary surfactant-associated protein C.Accordingly, it is presently believed that PRO813 polypeptide disclosedin the present application is a newly identified pulmonarysurfactant-associated protein C homolog.

[3131] 61. Full-length PRO809 Polypeptides

[3132] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO809. In particular, Applicants have identified andisolated cDNA encoding a PRO809 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA57836-1338 nucleotide sequence encodes a novel factor.

[3133] 62. Full-length PRO791 Polypeptides

[3134] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO791. In particular, Applicants have identified andisolated cDNA encoding a PRO791 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA57838-1337 nucleotide sequence encodes a novel factor; however, usingBLAST and FastA sequence alignment computer programs, there does appearto be some sequence identity with MHC-1 antigens, indicating that PRO791may be related thereto in structure and function.

[3135] 63. Full-length PRO1004 Polypeptides

[3136] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1004. In particular, cDNA encoding a PRO1004polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3137] As far as is known, the DNA57844-1410 sequence encodes a novelfactor designated herein as PRO1004. However, using WU-BLAST2 sequencealignment computer programs, some sequence identities with knownproteins were revealed.

[3138] 64. Full-length PRO1111 Polypeptides

[3139] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1111. In particular, cDNA encoding a PRO1111polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3140] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1111 (shown in FIG. 157 andSEQ ID NO:229) has certain amino acid sequence identity with LIG.Accordingly, it is presently believed that PRO1111 disclosed in thepresent application is a newly identified member of this glycoproteinfamily.

[3141] 65. Full-length PRO1344 Polypeptides

[3142] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1344. In particular, cDNA encoding a PRO1344polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3143] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1344 (shown in FIG. 159and SEQ ID NO:231) has certain amino acid sequence identity with thefactor C protein of Carcinoscorpius rotundicauda. Accordingly, it ispresently believed that PRO1344 disclosed in the present application isa newly identified factor C protein and may possess activity typical ofthat protein.

[3144] 66. Full-length PRO1109 Polypeptides

[3145] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1109. In particular, cDNA encoding a PRO1109polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3146] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1109 (shown in FIG. 161and SEQ ID NO:236) has certain amino acid sequence identity with thehuman UDP-Gal:GlcNAc galactosyltransferase protein. Accordingly, it ispresently believed that PRO1109 disclosed in the present application isa newly identified β-galactosyltransferase enzyme and has activitytypical of those enzymes.

[3147] 67. Full-length PRO1383 Polypeptides

[3148] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1383. In particular, cDNA encoding a PRO1383polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3149] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1383 (shown in FIG. 163and SEQ ID NO:241) has certain amino acid sequence identity with theputative human transmembrane protein nmb precursor (NMB_HUMAN).Accordingly, it is presently believed that PRO1383 disclosed in thepresent application is a newly identified nmb homolog.

[3150] 68. Full-length PRO1003 Polypeptides

[3151] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1003. In particular, Applicants have identified andisolated cDNA encoding a PRO1003 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO1003-encoding clone was isolatedfrom a human breast tumor tissue library. The PRO1003-encoding clone wasisolated using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the PRO1003-encoding clonemay encode a secreted factor. To Applicants present knowledge, theUNQ487 (DNA58846-1409) nucleotide sequence encodes a novel factor; usingBLAST and FastA sequence alignment computer programs, no sequenceidentities to any known proteins were revealed.

[3152] 69. Full-length PRO1108 Polypeptides

[3153] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1108. In particular, Applicants have identified andisolated cDNA encoding a PRO1108 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1108 polypeptide hassignificant similarity to the LPAAT protein. Accordingly, it ispresently believed that PRO1108 polypeptide disclosed in the presentapplication is a newly identified LPAAT homolog.

[3154] 70. Full-length PRO1137 Polypeptides

[3155] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1137. In particular, Applicants have identified andisolated cDNA encoding a PRO1137 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1137 polypeptide hassequence identity with ribosyltransferases. Accordingly, it is presentlybelieved that PRO1137 polypeptide disclosed in the present applicationis a newly identified member of the ribosyltransferase family andpossesses ribosyltransferase activity.

[3156] 71. Full-length PRO1138 Polypeptides

[3157] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1138. In particular, Applicants have identified andisolated cDNA encoding a PRO1138 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1138 polypeptide hassequence identity with CD84 leukocyte antigen. Accordingly, it ispresently believed that PRO1138 polypeptide disclosed in the presentapplication is a newly identified member of the Ig superfamily and hasactivity typical of other members of the Ig superfamily.

[3158] 72. Full-length PRO1054 Polypeptides

[3159] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1054. In particular, cDNA encoding a PRO1054polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3160] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1054 (shown in FIG. 174and SEQ ID NO:256) has amino acid sequence identity with one or more ofthe major urinary proteins. Accordingly, it is presently believed thatPRO1054 disclosed in the present application is a newly identifiedmember of the MUP family and may possess activity typical of thatfamily.

[3161] 73. Full-length PRO994 Polypeptides

[3162] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO994. In particular, cDNA encoding a PRO994 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3163] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO994 (shown in FIG. 176and SEQ ID NO:258) has amino acid sequence identity with thetumor-associated antigen L6. Accordingly, it is presently believed thatPRO994 disclosed in the present application is a newly identified L6antigen homolog.

[3164] 74. Full-length PRO812 Polypeptides

[3165] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO812. In particular, cDNA encoding a PRO812 polypeptidehas been identified and isolated, as disclosed in further detail in theExamples below.

[3166] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO812 (shown in FIG. 178and SEQ ID NO:260) has amino acid sequence identity with the prostaticsteroid-binding c1 protein. Accordingly, it is presently believed thatPRO812 disclosed in the present application is a newly identifiedprostatic steroid-binding c1 protein homolog.

[3167] 75. Full-length PRO1069 Polypeptides

[3168] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1069. In particular, Applicants have identified andisolated cDNA encoding a PRO1069 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, it was found that the PRO1069 polypeptide hassequence identity with CHIF. Accordingly, it is presently believed thatPRO1069 polypeptide disclosed in the present application is a newlyidentified CHIF polypeptide and is involved in ion conductance orregulation of ion conductance.

[3169] 76. Full-length PRO1129 Polypeptides

[3170] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1129. In particular, Applicants have identified andisolated cDNA encoding a PRO1129 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1129 polypeptide hassignificant similarity to the cytochrome P-450 family of proteins.Accordingly, it is presently believed that PRO1129 polypeptide disclosedin the present application is a newly identified member of thecytochrome P-450 family and possesses activity typical of that family.

[3171] 77. Full-length PRO1068 Polypeptides

[3172] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1068. In particular, cDNA encoding a PRO1068polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3173] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1068 has amino acid sequenceidentity with urotensin. Accordingly, it is presently believed thatPRO1068 disclosed in the present application is a newly identifiedmember of the urotensin family and may possess activity typical of theurotensin family.

[3174] 78. Full-length PRO1066 Polypeptides

[3175] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1066. In particular, Applicants have identified andisolated cDNA encoding a PRO1066 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO1066-encoding clone was isolatedfrom a human pancreatic tumor tissue library using a trapping techniquewhich selects for nucleotide sequences encoding secreted proteins. Thus,the PRO1066-encoding clone may encode a secreted factor. To Applicantspresent knowledge, the DNA59215-1425 nucleotide sequence encodes a novelfactor; using BLAST and FastA sequence alignment computer programs, nosequence identities to any known proteins were revealed.

[3176] 79. Full-length PRO1184 Polypeptides

[3177] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1184. In particular, Applicants have identified cDNAencoding a PRO1184 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59220-1514nucleotide sequence encodes a novel secreted factor.

[3178] 80. Full-length PRO1360 Polypeptides

[3179] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1360. In particular, cDNA encoding a PRO1360polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3180] As far as is known, the DNA59488-1603 sequence encodes a novelfactor designated herein as PRO1360; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed. Some sequence identities were revealed, asindicated below in the examples.

[3181] 81. Full-length PRO1029 Polypeptides

[3182] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1029. In particular, cDNA encoding a PRO1029polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3183] The DNA59493-1420 clone was isolated from a human fetal liverspleen library using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA59493-1420 clone doesencode a secreted factor. As far as is known, the DNA59493-1420 sequenceencodes a novel factor designated herein as PRO1029; using the WU-BLAST2sequence alignment computer program, no sequence identities to any knownproteins were revealed.

[3184] 82. Full-length PRO1139 Polypeptides

[3185] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1139. In particular, Applicants have identified andisolated cDNAs encoding PRO1139, as disclosed in further detail in theExamples below. Using BLAST and FastA sequence alignment computerprograms, Applicants found that the human PRO1139 protein originallyidentified exhibits a significant sequence homology to the a OB receptorassociated protein HSOBRGRP_(—)1, described by Bailleul et al., NucleicAcids Res. 25, 2752-2758 (1997) (EMBL Accession No: Y12670).

[3186] 83. Full-length PRO1309 Polypeptides

[3187] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1309. In particular, cDNA encoding a PRO1309polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3188] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1309 (shown in FIG. 196and SEQ ID NO:278) has certain amino acid sequence identity with aprotein designated KIAA0416, given the Dayhoff designationAB007876_(—)1. Moreover, PRO1309 has leucine rich repeats, accordingly,it is presently believed that PRO1309 disclosed in the presentapplication is a newly identified member of the leucine rich proteinfamily and may be involved in protein protein interactions.

[3189] 84. Full-length PRO1028 Polypeptides

[3190] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1028. In particular, Applicants have identified andisolated cDNA encoding a PRO1028 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA59603-1419 nucleotide sequence encodes a novel factor. BLAST andFastA sequence alignment computer programs showed some sequence identitywith proteins such as those designated “A53050” and EMU39529_(—)1”.

[3191] 85. Full-length PRO1027 Polypeptides

[3192] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1027. In particular, Applicants have identified andisolated cDNA encoding a PRO1027 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO1027-encoding clone was identifiedin a human uterine cervical tissue library. To Applicants presentknowledge, the DNA59605-1418 nucleotide sequence encodes a novel factor.

[3193] 86. Full-length PRO1107 Polypeptides

[3194] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1107. In particular, Applicants have identified andisolated cDNA encoding a PRO1107 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1107 polypeptide hassome similarity to the PC-1 protein, human insulin receptor tyrosinekinase inhibitor, an alkaline phosphodiesterase, and autotaxin.Accordingly, it is presently believed that PRO1107 polypeptide disclosedin the present application is a newly identified member of thephosphodiesterase family.

[3195] 87. Full-length PRO1140 Polypeptides

[3196] The present invention provides newly identified and isolatednucleotide sequences encoding novel multi-span transmembranepolypeptides referred to in the present application as PRO1140. Inparticular, Applicants have identified and isolated cDNA encoding aPRO1140 polypeptide, as disclosed in further detail in the Examplesbelow. Using BLAST and FastA sequence alignment computer programs, somesequence identity with known proteins was found.

[3197] 88. Full-length PRO1106 Polypeptides

[3198] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1106. In particular, Applicants have identified andisolated cDNA encoding a PRO1106 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO1106 polypeptide hassignificant similarity to the peroxisomal calcium-dependent solutecarrier. Accordingly, it is presently believed that PRO1106 polypeptidedisclosed in the present application is a newly identified member of themitochondrial carrier superfamily and possesses transporter activitytypical of this family.

[3199] 89. Full-length PRO1291 Polypeptides

[3200] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1291. In particular, cDNA encoding a PRO1291polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3201] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1291 (shown in FIG. 208and SEQ ID NO:291) has certain amino acid sequence identity with thebutyrophilin protein. Accordingly, it is presently believed that PRO1291disclosed in the present application is a newly identified butyrophilinhomolog and may possess activity typical of that protein.

[3202] 90. Full-length PRO1105 Polypeptides

[3203] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1105. In particular, Applicants have identified cDNAencoding a PRO1105 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59612-1466nucleotide sequence encodes a novel factor. There is, however, somesequence identity with a peroxydase precursor designated in a Dayhoffdatabase as “ATTS1623_(—)1”.

[3204] 91. Full-length PRO511 Polypeptides

[3205] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO511. In particular, Applicants have identified andisolated cDNA encoding a PRO511 polypeptide, as disclosed in furtherdetail in the Examples below. The PRO511-encoding clone was isolatedfrom a human colon tissue library. To Applicants present knowledge, theDNA59613-1417 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, sequence identities withRoBo-1, phospholipase inhibitors and a protein designated as“SSC20F10_(—)1” were revealed, indicated that PRO511 may be related toone or more of these proteins.

[3206] 92. Full-length PRO1104 Polypeptides

[3207] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1104. In particular, Applicants have identified andisolated cDNA encoding a PRO1104 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA59616-1465 nucleotide sequence encodes a novel factor; using BLASTand FastA sequence alignment computer programs, some sequence identityappeared with proteins designated as “AB002107_(—)1”, “AF022991_(—)1”and “SP96_DICDI”.

[3208] 93. Full-length PRO1100 Polypeptides

[3209] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1100. In particular, Applicants have identified cDNAencoding a PRO1100 polypeptide, as disclosed in further detail in theExamples below. To Applicants present knowledge, the DNA59619-1464nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, only some sequence identity withknown proteins was revealed. There is some sequence identity with theyeast hypothetical 42.5 KD protein in TSM1-ARE1 intergenic region(ACCESSION NO:140496), designated “YSCT4_YEAST”.

[3210] 94. Full-length PRO836 Polypeptides

[3211] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO836. In particular, Applicants have identified andisolated cDNA encoding a PRO836 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA59620-1463 nucleotide sequence encodes a novel factor. Using BLASTand FastA sequence alignment computer programs, there appears to be somesequence identity with SLS1.

[3212] 95. Full-length PRO1141 Polypeptides

[3213] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1141. In particular, cDNA encoding a PRO1141polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3214] The DNA59625-1498 clone was isolated from a human ileum tissuelibrary. As far as is known, the DNA59625-1498 sequence encodes a novelfactor designated herein as PRO1141; using the WU-BLAST2 sequencealignment computer program, no sequence identities to any known proteinswere revealed.

[3215] 96. Full-length PRO1132 Polypeptides

[3216] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1132. In particular, cDNA encoding a PRO1132polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3217] Using WU-BLAST2 sequence alignment computer program, it has beenfound that a full-length native sequence PRO1132 (shown in FIG. 226 andSEQ ID NO:309) has certain amino acid sequence identity with enamelmatrix serine proteinase 1 and neuropsin. Accordingly, it is presentlybelieved that PRO1132 disclosed in the present application is a newlyidentified member of the serine protease family and may possess proteaseactivity typical of this family.

[3218] 97. Full-length PRO1346 Polypeptides

[3219] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as NL7 (UNQ701). In particular, cDNA encoding an NL7polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3220] As disclosed in the Examples below, a clone DNA59776-1600 hasbeen deposited with ATCC. The actual nucleotide sequence of the clonecan be readily determined by the skilled artisan by sequencing of thedeposited clone using routine methods in the art. The predicted aminoacid sequence can be determined from the nucleotide sequence usingroutine skill. For the NL7 (PRO1346) herein, Applicants have identifiedwhat is believed to be the reading frame best identifiable with thesequence information available at the time of filing.

[3221] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence NL7 (shown in FIG. 228 and SEQID NO:314) has certain amino acid sequence identity withmicrofibril-associated glycoprotein 4 (MFA4_HUMAN); ficolin-A—Musmusculus (AB007813_(—)1); human lectin P35 (D63155S6_(—)1); ficolinB—Mus musculus (AF0063217_(—)1); human tenascin-R (restriction)(HS518E13_(—)1); the long form of a rat janusin precursor (A45445);fibrinogen-related protein HFREP-1 precursor (JNO596); a human Tenascinprecursor (TENA HUMAN); human CDT6 (HSY16132_(—)1); andangiopoietin-1—Mus musculus (MMU83509_(—)1). It is presently believedthat NL7 disclosed in the present application is a novel TIE ligandhomologue, and may play a role in angiogenesis and/or vascularmaintenance and/pr wound healing and/or inflammation and/or tumordevelopment and/or growth

[3222] 98. Full-length PRO1131 Polypeptides

[3223] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1131. In particular, cDNA encoding a PRO1131polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3224] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1131 (shown in FIG. 230 andSEQ ID NO:319) has certain amino acid sequence identity with alectin-like oxidized LDL receptor. Accordingly, it is presently believedthat PRO1131 disclosed in the present application may have at least onemechanism similar to those of the LDL receptors.

[3225] 99. Full-length PRO1281 Polypeptides

[3226] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1281. In particular, cDNA encoding a PRO1281polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3227] The DNA59820-1549 clone was isolated from a human fetal liverlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, as far as is known, theDNA59820-1549 sequence encodes a novel factor designated herein asPRO1281. Using WU-BLAST2 sequence alignment computer programs, somesequence identities to known proteins was found, but determined not tobe significant.

[3228] 100. Full-length PRO1064 Polypeptides

[3229] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1064. In particular, cDNA encoding a PRO1064polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3230] The DNA59827-1426 clone was isolated from a human fetal kidneylibrary. As far as is known, the DNA59827-1426 sequence encodes a novelfactor designated herein as PRO1064; using the WU-BLAST2 sequencealignment computer program, no significant sequence identities to anyknown proteins were revealed.

[3231] 101. Full-length PRO1379 Polypeptides

[3232] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1379. In particular, cDNA encoding a PRO1379polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3233] The DNA59828 clone was isolated from a human fetal kidneylibrary. As far as is known, the PRO1379 polypeptide encoded thereby isa novel secreted factor. Using WU-BLAST2 sequence alignment computerprograms, sequence identity was found between PRO1379 and a hypotheticalyeast protein “YHY8_YEAST” (Dayhoff database; version 35.45 SwissProt35), particularly at the C-terminal ends. Sequence homologies with otherknown proteins were revealed, but determined not to be significant.

[3234] 102. Full-length PRO844 Polypeptides

[3235] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO844. In particular, Applicants have identified andisolated cDNA encoding a PRO844 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO844 polypeptide hassequence identity with serine protease inhibitors. Accordingly, it ispresently believed that PRO844 polypeptide disclosed in the presentapplication is a newly identified serine protease inhibitor and iscapable of inhibiting serine proteases.

[3236] 103. Full-length PRO848 Polypeptides

[3237] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO848. In particular, Applicants have identified andisolated cDNA encoding a PRO848 polypeptide, as disclosed in furtherdetail in the Examples below. Using BLAST and FastA sequence alignmentcomputer programs, Applicants found that the PRO848 polypeptide hassequence identity with sialyltransferases. Accordingly, it is presentlybelieved that PRO848 polypeptide disclosed in the present application isa newly identified member of the sialyltransferase family and possessessialylation capabilities as typical of this family.

[3238] 104. Full-length PRO1097 Polypeptides

[3239] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1097. In particular, Applicants have identified andisolated cDNA encoding a PRO1097 polypeptide, as disclosed in furtherdetail in the Examples below. To Applicants present knowledge, theDNA59841-1460 nucleotide sequence encodes a novel factor. Using BLASTand FastA sequence alignment computer programs, some sequence identitywith proteins designated as “CELK05G3_(—)3”, “CRU26344_(—)1”,“SPBC16C6_(—)8”, “P_W13844” and “AF013403” was revealed.

[3240] 105. Full-length PRO1153 Polypeptides

[3241] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1153. In particular, cDNA encoding a PRO1153polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3242] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1153 (shown in FIG. 246 andSEQ ID NO:351) has certain amino acid sequence identity with HPBRII-7protein submitted to the EMBL Data Library June 1992. Accordingly, it ispresently believed that PRO1153 disclosed in the present application maybe related to HPBRII-7.

[3243] 106. Full-length PRO1154 Polypeptides

[3244] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1154. In particular, cDNA encoding a PRO1154polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3245] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1154 (shown in FIG. 248 andSEQ ID NO:353) aligns with a KIAA0525 protein, designated AB011097.PRO1154 has a novel N-terminus of 73 amino acids. Accordingly, PRO1154is believed to be novel. PRO1154 also has significant sequence identitywith aminopeptidase N, insulin-regulated membrane aminopeptidase,throtropin-releasing hormone degrading enzyme and placental leucineaminopeptidase. Therefore, PRO1154 is believed to be a novelaminopeptidase, or peptide which degrades peptides.

[3246] 107. Full-length PRO1181 Polypeptides

[3247] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1181. In particular, cDNA encoding a PRO1181polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3248] The DNA59847-1511 clone was isolated from a human prostate tissuelibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA59847-1511 clone doesencode a secreted factor. As far as is known, the DNA59847-1511 sequenceencodes a novel factor designated herein as PRO1181; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3249] 108. Full-length PRO1182 Polypeptides

[3250] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1182. In particular, cDNA encoding a PRO1182polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3251] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1182 (shown in FIG. 252and SEQ ID NO:357) has amino acid sequence identity with the conglutininprotein. Accordingly, it is presently believed that PRO1182 disclosed inthe present application is a newly identified conglutinin homolog.

[3252] 109. Full-length PRO1155 Polypeptides

[3253] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1155. In particular, cDNA encoding a PRO1155polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3254] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1155 (shown in FIG. 254 andSEQ ID NO:359) has certain amino acid sequence identity with neurokininB. Accordingly, it is presently believed that PRO1155 disclosed in thepresent application is a newly identified member of the tachykininfamily.

[3255] 110. Full-length PRO1156 Polypeptides

[3256] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1156. In particular, cDNA encoding a PRO1156polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3257] The DNA59853-1505 clone was isolated from an adult human heartlibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA59853-1505 clone mayencode a secreted factor. As far as is known, the DNA59853-1505 sequenceencodes a novel factor designated herein as PRO1156. However, usingWU-BLAST2 sequence alignment computer programs, some sequence identitywith known proteins were revealed.

[3258] 111. Full-length PRO1098 Polypeptides

[3259] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1098. In particular, Applicants have identified cDNAencoding a PRO1098 polypeptide, as disclosed in further detail in theExamples below. The PRO1098-encoding clone was isolated from a humanlung tissue library. To Applicants present knowledge, the DNA59854-1459nucleotide sequence encodes a novel factor; using BLAST and FastAsequence alignment computer programs, no significant sequence identitiesto any known proteins were revealed. Some sequence identity appearedwith proteins such as the “Env” polyprotein and a methyltransferase.

[3260] 112. Full-length PRO1127 Polypeptides

[3261] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1127. In particular, cDNA encoding a PRO1127polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3262] The DNA60283-1484 clone encodes a secreted factor. As far as isknown, the DNA60283-1484 sequence encodes a novel factor designatedherein as PRO1127; using WU-BLAST2 sequence alignment computer programs,minimal sequence identities to any known proteins were revealed.

[3263] 113. Full-length PRO1126 Polypeptides

[3264] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1126. In particular, cDNA encoding a PRO1126polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3265] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1126 (shown in FIG. 262and SEQ ID NO:367) has certain amino acid sequence identity with theolfactomedin protein. Accordingly, it is presently believed that PRO1126disclosed in the present application is a newly identified olfactomedinhomolog and may possess activity typical of that protein.

[3266] 114. Full-length PRO1125 Polypeptides

[3267] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1125. In particular, cDNA encoding a PRO1125polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3268] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1125 (shown in FIG. 264 andSEQ ID NO:369) has certain amino acid sequence identity withtranscriptional repressor rco-1. Accordingly, it is presently believedthat PRO1125 disclosed in the present application is a newly identifiedmember of the WD superfamily.

[3269] 115. Full-length PRO1186 Polypeptides

[3270] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1186. In particular, cDNA encoding a PRO1186polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3271] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1186 (shown in FIG. 266 andSEQ ID NO:371) has amino acid sequence identity with venom protein Afrom Dendroaspis polylepsis polylepsis venom. Accordingly, it ispresently believed that PRO1186 disclosed in the present application isa newly identified member of venom protein A and may share a relatedmechanism.

[3272] 116. Full-length PRO1198 Polypeptides

[3273] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1198. In particular, cDNA encoding a PRO1198polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3274] As far as is known, the DNA60622-1525 sequence encodes a novelfactor designated herein as PRO1198. However, using WU-BLAST2 sequencealignment computer programs, some sequence identity with known proteinswas found.

[3275] 117. Full-length PRO1158 Polypeptides

[3276] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1158. In particular, cDNA encoding a PRO1158polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3277] The DNA60625-1507 clone was isolated from a human lung tumortissue library. As far as is known, the DNA60625-1507 sequence encodes anovel factor designated herein as PRO1158. However, using WU-BLAST2sequence alignment computer programs, some sequence identities withknown proteins were shown.

[3278] 118. Full-length PRO1159 Polypeptides

[3279] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1159. In particular, cDNA encoding a PRO1159polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3280] The DNA60627-1508 clone was isolated from a human peripheralblood granulocyte tissue library using a trapping technique whichselects for nucleotide sequences encoding secreted proteins. Thus, theDNA60627-1508 clone does encode a secreted factor. As far as is known,the DNA60627-1508 sequence encodes a novel factor designated herein asPRO1159; using the WU-BLAST2 sequence alignment computer program, nosequence identities to any known proteins were revealed.

[3281] 119. Full-length PRO1124 Polypeptides

[3282] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1124. In particular, cDNA encoding a PRO1124polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3283] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1124 (shown in FIG. 274 andSEQ ID NO:377) has amino acid sequence identity with an epithelialchloride channel protein from bos taurus. PRO1124 also has sequenceidentity with ECAM-1. Accordingly, it is presently believed that PRO1124disclosed in the present application is a newly identified cell membraneprotein involved in communication of cells either through ion channelsor cell adhesion molecules.

[3284] 120. Full-length PRO1287 Polypeptides

[3285] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1287. In particular, cDNA encoding a PRO1287polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3286] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1287 (shown in FIG. 276and SEQ ID NO:381) has amino acid sequence identity with the radicalfringe protein from Gallus gallus (GGU82088_(—)1). Accordingly, it ispresently believed that PRO1287 disclosed in the present application isa newly identified fringe protein homolog and may possess activitytypical of the fringe protein.

[3287] 121. Full-length PRO1312 Polypeptides

[3288] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1312. In particular, cDNA encoding a PRO1312polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3289] Using WU-BLAST2 sequence alignment computer programs, somesequence identities with known proteins were revealed, but weredetermined not to be significant. Therefore, as far as is known, theDNA61873-1574 sequence encodes a novel transmembrane protein designatedherein as PRO1312.

[3290] 122. Full-length PRO1192 Polypeptides

[3291] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1192. In particular, cDNA encoding a PRO1192polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3292] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1192 (shown in FIG. 280 andSEQ ID NO:389) has amino acid sequence identity with trout P0-likeglycoprotein (GEN12838 IP1). Accordingly, it is presently believed thatPRO1192 disclosed in the present application is a newly identifiedmember of the myelin P0 glycoprotein family.

[3293] 123. Full-length PRO1160 Polypeptides

[3294] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1160. In particular, cDNA encoding a PRO1160polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3295] The DNA62872-1509 clone was isolated from a human breast tissuelibrary using a trapping technique which selects for nucleotidesequences encoding secreted proteins. Thus, the DNA62872-1509 clone doesencode a secreted factor. As far as is known, the DNA62872-1509 sequenceencodes a novel factor designated herein as PRO1160; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3296] 124. Full-length PRO1187 Polypeptides

[3297] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1187. In particular, cDNA encoding a PRO1187polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3298] As far as is known, the DNA62876-1517 sequence encodes a novelfactor designated herein as PRO1187; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed.

[3299] 125. Full-length PRO1185 Polypeptides

[3300] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1185. In particular, cDNA encoding a PRO1185polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3301] As far as is known, the DNA62881-1515 clone encodes a novelfactor designated herein as PRO1185; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed.

[3302] 126. Full-length PRO1345 Polypeptides

[3303] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1345. In particular, cDNA encoding a PRO1345polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3304] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1345 (shown in FIG. 288and SEQ ID NO:403) has amino acid sequence identity with the C-typelectin homolog precursor protein of bos taurus (BTU22298_(—)1).Accordingly, it is presently believed that PRO1345 disclosed in thepresent application is a newly identified member of the C-type lectinprotein family and may possess activity typical of that family or of thetetranectin protein in particular.

[3305] 127. Full-length PRO1245 Polypeptides

[3306] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1245. In particular, cDNA encoding a PRO1245polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3307] The DNA64884-1527 clone was identified using methods that selectsfor nucleotide sequences encoding secreted proteins. As far as is known,the DNA64884-1527 sequence encodes a novel secreted factor designatedherein as PRO1245. Using WU-BLAST2 sequence alignment computer programs,some sequence identities to known proteins were revealed; however, itwas determined that they were not significant.

[3308] 128. Full-length PRO1358 Polypeptides

[3309] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1358. In particular, cDNA encoding a PRO1358polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3310] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1358 (shown in FIG. 292 andSEQ ID NO:410) has amino acid sequence identity with RASP-1.Accordingly, it is presently believed that PRO1358 disclosed in thepresent application is a newly identified member of the serpin family ofserine protease inhibitors and may possess serine protease inhibitionactivity, protein catabolism inhibitory activity and/or be associatedwith regeneration of tissue.

[3311] 129. Full-length PRO1195 Polypeptides

[3312] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1195. In particular, cDNA encoding a PRO1195polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3313] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1195 (shown in FIG. 294 andSEQ ID NO:412) has amino acid sequence identity with MMU28486_(—)1,termed a proline rich acidic protein from Mus musculus, locus MMU28486,Accession: U28486, database GBTRANS, submitted 06-JUN-1995 by John W.Kasik. Accordingly, it is presently believed that PRO1195 disclosed inthe present application is a newly identified member of this proteinfamily.

[3314] 130. Full-length PRO1270 Polypeptides

[3315] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1270. In particular, cDNA encoding a PRO1270polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3316] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1270 (shown in FIG. 296and SEQ ID NO:414) has amino acid sequence identity with the lectinprotein (XLU86699_(—)1) of Xenopus laevis. Accordingly, it is presentlybelieved that PRO1270 disclosed in the present application is a newlyidentified member of the lectin protein family and may possess activitytypical of that family.

[3317] 131. Full-length PRO1271 Polypeptides

[3318] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1271. In particular, cDNA encoding a PRO1271polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3319] As far as is known, the DNA66309-1538 sequence encodes a novelfactor designated herein as PRO1271; using WU-BLAST2 sequence alignmentcomputer programs, no significant sequence identities to any knownproteins were revealed (results further described in the examplesbelow).

[3320] 132. Full-length PRO1375 Polypeptides

[3321] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1375. In particular, cDNA encoding a PRO1375polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3322] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1375 (shown in FIG. 300 andSEQ ID NO:418) has amino acid sequence identity PUT2. Accordingly, it ispresently believed that PRO1375 disclosed in the present application hasat least one related mechanism of PUT2.

[3323] 133. Full-length PRO1385 Polypeptides

[3324] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1385. In particular, cDNA encoding a PRO1385polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3325] The DNA68869-1610 clone was isolated from a human tissue libraryusing a trapping technique which selects for nucleotide sequencesencoding secreted proteins. Thus, the DNA68869-1610 clone does encode asecreted factor. As far as is known, the DNA68869-1610 sequence encodesa novel factor designated herein as PRO1385; using the WU-BLAST2sequence alignment computer program, no significant sequence identitiesto any known proteins were revealed.

[3326] 134. Full-length PRO1387 Polypeptides

[3327] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1387. In particular, cDNA encoding a PRO1387polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3328] Using the WU-BLAST2 sequence alignment computer program, it hasbeen found that a full-length native sequence PRO1387 (shown in FIG. 304and SEQ ID NO:422) has amino acid sequence identity with the myelin p0protein protein precursor (MYP0_HETFR). Accordingly, it is presentlybelieved that PRO1387 disclosed in the present application is a newlyidentified member of the myelin protein family and may possess activitytypical of that family.

[3329] 135. Full-length PRO1384 Polypeptides

[3330] The present invention provides newly identified and isolatednucleotide sequences encoding polypeptides referred to in the presentapplication as PRO1384. In particular, cDNA encoding a PRO1384polypeptide has been identified and isolated, as disclosed in furtherdetail in the Examples below.

[3331] Using WU-BLAST2 sequence alignment computer programs, it has beenfound that a full-length native sequence PRO1384 (shown in FIG. 306 andSEQ ID NO:424) has amino acid sequence identity with NKG2-D(AF054819_(—)1; Dayhoff database, version 35.45 SwissProt 35).Accordingly, it is presently believed that PRO1384 disclosed in thepresent application is a newly identified member of the NKG2 family andmay possess MHC activation/inactivation activities typical of the NKG2family.

[3332] B. PRO Polypeptide Variants

[3333] In addition to the full-length native sequence PRO polypeptidesdescribed herein, it is contemplated that PRO variants can be prepared.PRO variants can be prepared by introducing appropriate nucleotidechanges into the PRO DNA, and/or by synthesis of the desired PROpolypeptide. Those skilled in the art will appreciate that amino acidchanges may alter post-translational processes of the PRO, such aschanging the number or position of glycosylation sites or altering themembrane anchoring characteristics.

[3334] Variations in the native full-length sequence PRO or in variousdomains of the PRO described herein, can be made, for example, using anyof the techniques and guidelines for conservative and non-conservativemutations set forth, for instance, in U.S. Pat. No. 5,364,934.Variations may be a substitution, deletion or insertion of one or morecodons encoding the PRO that results in a change in the amino acidsequence of the PRO as compared with the native sequence PRO. Optionallythe variation is by substitution of at least one amino acid with anyother amino acid in one or more of the domains of the PRO. Guidance indetermining which amino acid residue may be inserted, substituted ordeleted without adversely affecting the desired activity may be found bycomparing the sequence of the PRO with that of homologous known proteinmolecules and minimizing the number of amino acid sequence changes madein regions of high homology. Amino acid substitutions can be the resultof replacing one amino acid with another amino acid having similarstructural and/or chemical properties, such as the replacement of aleucine with a serine, i.e., conservative amino acid replacements.Insertions or deletions may optionally be in the range of about 1 to 5amino acids. The variation allowed may be determined by systematicallymaking insertions, deletions or substitutions of amino acids in thesequence and testing the resulting variants for activity exhibited bythe full-length or mature native sequence.

[3335] PRO polypeptide fragments are provided herein. Such fragments maybe truncated at the N-terminus or C-terminus, or may lack internalresidues, for example, when compared with a full length native protein.Certain fragments lack amino acid residues that are not essential for adesired biological activity of the PRO polypeptide.

[3336] PRO fragments may be prepared by any of a number of conventionaltechniques. Desired peptide fragments may be chemically synthesized. Analternative approach involves generating PRO fragments by enzymaticdigestion, e.g., by treating the protein with an enzyme known to cleaveproteins at sites defined by particular amino acid residues, or bydigesting the DNA with suitable restriction enzymes and isolating thedesired fragment. Yet another suitable technique involves isolating andamplifying a DNA fragment encoding a desired polypeptide fragment, bypolymerase chain reaction (PCR). Oligonucleotides that define thedesired termini of the DNA fragment are employed at the 5′ and 3′primers in the PCR. Preferably, PRO polypeptide fragments share at leastone biological and/or immunological activity with the native PROpolypeptide disclosed herein.

[3337] In particular embodiments, conservative substitutions of interestare shown in Table 6 under the heading of preferred substitutions. Ifsuch substitutions result in a change in biological activity, then moresubstantial changes, denominated exemplary substitutions in Table 6, oras further described below in reference to amino acid classes, areintroduced and the products screened. TABLE 6 Original ExemplaryPreferred Residue Substitutions Substitutions Ala (A) val; leu; ile valArg (R) lys; gln; asn lys Asn (N) gln; his; lys; arg gln Asp (D) glu gluCys (C) ser ser Gln (Q) asn asn Glu (E) asp asp Gly (G) pro; ala ala His(H) asn; gln; lys; arg arg Ile (I) leu; val; met; ala; phe; norleucineleu Leu (L) norleucine; ile; val; met; ala; phe ile Lys (K) arg; gln;asn arg Met (M) leu; phe; ile leu Phe (F) leu; val; ile; ala; tyr leuPro (P) ala ala Ser (S) thr thr Thr (T) ser ser Trp (W) tyr; phe tyr Tyr(Y) trp; phe; thr; ser phe Val (V) ile; leu; met; phe; ala; norleucineleu

[3338] Substantial modifications in function or immunological identityof the PRO polypeptide are accomplished by selecting substitutions thatdiffer significantly in their effect on maintaining (a) the structure ofthe polypeptide backbone in the area of the substitution, for example,as a sheet or helical conformation, (b) the charge or hydrophobicity ofthe molecule at the target site, or (c) the bulk of the side chain.Naturally occurring residues are divided into groups based on commonside-chain properties:

[3339] (1) hydrophobic: norleucine, met, ala, val, leu, ile;

[3340] (2) neutral hydrophilic: cys, ser, thr;

[3341] (3) acidic: asp, glu;

[3342] (4) basic: asn, gin, his, lys, arg;

[3343] (5) residues that influence chain orientation: gly, pro; and

[3344] (6) aromatic: trp, tyr, phe.

[3345] Non-conservative substitutions will entail exchanging a member ofone of these classes for another class. Such substituted residues alsomay be introduced into the conservative substitution sites or, morepreferably, into the remaining (non-conserved) sites.

[3346] The variations can be made using methods known in the art such asoligonucleotide-mediated (site-directed) mutagenesis, alanine scanning,and PCR mutagenesis. Site-directed mutagenesis [Carter et al., Nucl.Acids Res., 13:4331 (1986); Zoller et al., Nucl. Acids Res., 10:6487(1987)], cassette mutagenesis [Wells et al., Gene, 34:315 (1985)],restriction selection mutagenesis [Wells et al., Philos. Trans. R. Soc.London SerA, 317:415 (1986)] or other known techniques can be performedon the cloned DNA to produce the PRO variant DNA.

[3347] Scanning amino acid analysis can also be employed to identify oneor more amino acids along a contiguous sequence. Among the preferredscanning amino acids are relatively small, neutral amino acids. Suchamino acids include alanine, glycine, serine, and cysteine. Alanine istypically a preferred scanning amino acid among this group because iteliminates the side-chain beyond the beta-carbon and is less likely toalter the main-chain conformation of the variant [Cunningham and Wells,Science, 244: 1081-1085 (1989)]. Alanine is also typically preferredbecause it is the most common amino acid. Further, it is frequentlyfound in both buried and exposed positions [Creighton, The Proteins,(W.H. Freeman & Co., N.Y.); Chothia, J. Mol. Biol., 150:1 (1976)]. Ifalanine substitution does not yield adequate amounts of variant, anisoteric amino acid can be used.

[3348] C. Modifications of PRO

[3349] Covalent modifications of PRO are included within the scope ofthis invention. One type of covalent modification includes reactingtargeted amino acid residues of a PRO polypeptide with an organicderivatizing agent that is capable of reacting with selected side chainsor the N- or C-terminal residues of the PRO. Derivatization withbifunctional agents is useful, for instance, for crosslinking PRO to awater-insoluble support matrix or surface for use in the method forpurifying anti-PRO antibodies, and vice-versa. Commonly usedcrosslinking agents include, e.g., 1,1-bis(diazoacetyl)-2-phenylethane,glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with4-azidosalicylic acid, homobifunctional imidoesters, includingdisuccinimidyl esters such as 3,3′-dithiobis(succinimidylpropionate),bifunctional maleimides such as bis-N-maleimido-1,8-octane and agentssuch as methyl-3-[(p-azidophenyl)dithio]propioimidate.

[3350] Other modifications include deamidation of glutaminyl andasparaginyl residues to the corresponding glutamyl and aspartylresidues, respectively, hydroxylation of proline and lysine,phosphorylation of hydroxyl groups of seryl or threonyl residues,methylation of the α-amino groups of lysine, arginine, and histidineside chains [T. E. Creighton, Proteins: Structure and MolecularProperties, W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)],acetylation of the N-terminal amine, and amidation of any C-terminalcarboxyl group.

[3351] Another type of covalent modification of the PRO polypeptideincluded within the scope of this invention comprises altering thenative glycosylation pattern of the polypeptide. Altering the nativeglycosylation pattern” is intended for purposes herein to mean deletingone or more carbohydrate moieties found in native sequence PRO (eitherby removing the underlying glycosylation site or by deleting theglycosylation by chemical and/or enzymatic means), and/or adding one ormore glycosylation sites that are not present in the native sequencePRO. In addition, the phrase includes qualitative changes in theglycosylation of the native proteins, involving a change in the natureand proportions of the various carbohydrate moieties present.

[3352] Addition of glycosylation sites to the PRO polypeptide may beaccomplished by altering the amino acid sequence. The alteration may bemade, for example, by the addition of, or substitution by, one or moreserine or threonine residues to the native sequence PRO (for O-linkedglycosylation sites). The PRO amino acid sequence may optionally bealtered through changes at the DNA level, particularly by mutating theDNA encoding the PRO polypeptide at preselected bases such that codonsare generated that will translate into the desired amino acids.

[3353] Another means of increasing the number of carbohydrate moietieson the PRO polypeptide is by chemical or enzymatic coupling ofglycosides to the polypeptide. Such methods are described in the art,e.g., in WO 87/05330 published Sep. 11, 1987, and in Aplin and Wriston,CRC Crit. Rev. Biochem., pp. 259-306 (1981).

[3354] Removal of carbohydrate moieties present on the PRO polypeptidemay be accomplished chemically or enzymatically or by mutationalsubstitution of codons encoding for amino acid residues that serve astargets for glycosylation. Chemical deglycosylation techniques are knownin the art and described, for instance, by Hakimuddin, et al., Arch.Biochem. Biophys., 259:52 (1987) and by Edge et al., Anal. Biochem.,118:131 (1981). Enzymatic cleavage of carbohydrate moieties onpolypeptides can be achieved by the use of a variety of endo- andexo-glycosidases as described by Thotakura et al., Meth. Enzymol.,138:350 (1987).

[3355] Another type of covalent modification of PRO comprises linkingthe PRO polypeptide to one of a variety of nonproteinaceous polymers,e.g., polyethylene glycol (PEG), polypropylene glycol, orpolyoxyalkylenes, in the manner set forth in U.S. Pat. Nos. 4,640,835;4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337.

[3356] The PRO of the present invention may also be modified in a way toform a chimeric molecule comprising PRO fused to another, heterologouspolypeptide or amino acid sequence.

[3357] In one embodiment, such a chimeric molecule comprises a fusion ofthe PRO with a tag polypeptide which provides an epitope to which ananti-tag antibody can selectively bind. The epitope tag is generallyplaced at the amino- or carboxyl-terminus of the PRO. The presence ofsuch epitope-tagged forms of the PRO can be detected using an antibodyagainst the tag polypeptide. Also, provision of the epitope tag enablesthe PRO to be readily purified by affinity purification using ananti-tag antibody or another type of affinity matrix that binds to theepitope tag. Various tag polypeptides and their respective antibodiesare well known in the art. Examples include poly-histidine (poly-his) orpoly-histidine-glycine (poly-his-gly) tags; the flu HA tag polypeptideand its antibody 12CA5 [Field et al., Mol. Cell. Biol., 8:2159-2165(1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10antibodies thereto [Evan et al., Molecular and Cellular Biology,5:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD)tag and its antibody [Paborsky et al., Protein Engineering, 3(6):547-553(1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al.,BioTechnology, 6:1204-1210 (1988)]; the KT3 epitope peptide [Martin etal., Science, 255:192-194 (1992)]; an α-tubulin epitope peptide [Skinneret al., J. Biol. Chem., 266:15163-15166 (1991)]; and the T7 gene 10protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci. USA,87:6393-6397 (1990)].

[3358] In an alternative embodiment, the chimeric molecule may comprisea fusion of the PRO with an immunoglobulin or a particular region of animmunoglobulin. For a bivalent form of the chimeric molecule (alsoreferred to as an “immunoadhesin”), such a fusion could be to the Fcregion of an IgG molecule. The Ig fusions preferably include thesubstitution of a soluble (transmembrane domain deleted or inactivated)form of a PRO polypeptide in place of at least one variable regionwithin an Ig molecule. In a particularly preferred embodiment, theimmunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge,CH1, CH2 and CH3 regions of an IgG1 molecule. For the production ofimmunoglobulin fusions see also U.S. Pat. No. 5,428,130 issued Jun. 27,1995.

[3359] D. Preparation of PRO

[3360] The description below relates primarily to production of PRO byculturing cells transformed or transfected with a vector containing PROnucleic acid. It is, of course, contemplated that alternative methods,which are well known in the art, may be employed to prepare PRO. Forinstance, the PRO sequence, or portions thereof, may be produced bydirect peptide synthesis using solid-phase techniques [see, e.g.,Stewart et al., Solid-Phase Peptide Synthesis, W.H. Freeman Co., SanFrancisco, Calif. (1969); Merrifield, J. Am. Chem. Soc., 85:2149-2154(1963)]. In vitro protein synthesis may be performed using manualtechniques or by automation. Automated synthesis may be accomplished,for instance, using an Applied Biosystems Peptide Synthesizer (FosterCity, Calif.) using manufacturer's instructions. Various portions of thePRO may be chemically synthesized separately and combined using chemicalor enzymatic methods to produce the full-length PRO.

[3361] 1. Isolation of DNA Encoding PRO

[3362] DNA encoding PRO may be obtained from a cDNA library preparedfrom tissue believed to possess the PRO mRNA and to express it at adetectable level. Accordingly, human PRO DNA can be convenientlyobtained from a cDNA library prepared from human tissue, such asdescribed in the Examples. The PRO-encoding gene may also be obtainedfrom a genomic library or by known synthetic procedures (e.g., automatednucleic acid synthesis).

[3363] Libraries can be screened with probes (such as antibodies to thePRO or oligonucleotides of at least about 20-80 bases) designed toidentify the gene of interest or the protein encoded by it. Screeningthe cDNA or genomic library with the selected probe may be conductedusing standard procedures, such as described in Sambrook et al.,Molecular Cloning: A Laboratory Manual (New York: Cold Spring HarborLaboratory Press, 1989). An alternative means to isolate the geneencoding PRO is to use PCR methodology [Sambrook et al., supra;Dieffenbach et al., PCR Primer: A Laboratory Manual (Cold Spring HarborLaboratory Press, 1995)].

[3364] The Examples below describe techniques for screening a cDNAlibrary. The oligonucleotide sequences selected as probes should be ofsufficient length and sufficiently unambiguous that false positives areminimized. The oligonucleotide is preferably labeled such that it can bedetected upon hybridization to DNA in the library being screened.Methods of labeling are well known in the art, and include the use ofradiolabels like ³²P-labeled ATP, biotinylation or enzyme labeling.Hybridization conditions, including moderate stringency and highstringency, are provided in Sambrook et al., supra.

[3365] Sequences identified in such library screening methods can becompared and aligned to other known sequences deposited and available inpublic databases such as GenBank or other private sequence databases.Sequence identity (at either the amino acid or nucleotide level) withindefined regions of the molecule or across the full-length sequence canbe determined using methods known in the art and as described herein.

[3366] Nucleic acid having protein coding sequence may be obtained byscreening selected cDNA or genomic libraries using the deduced aminoacid sequence disclosed herein for the first time, and, if necessary,using conventional primer extension procedures as described in Sambrooket al., supra, to detect precursors and processing intermediates of mRNAthat may not have been reverse-transcribed into cDNA.

[3367] 2. Selection and Transformation of Host Cells

[3368] Host cells are transfected or transformed with expression orcloning vectors described herein for PRO production and cultured inconventional nutrient media modified as appropriate for inducingpromoters, selecting transformants, or amplifying the genes encoding thedesired sequences. The culture conditions, such as media, temperature,pH and the like, can be selected by the skilled artisan without undueexperimentation. In general, principles, protocols, and practicaltechniques for maximizing the productivity of cell cultures can be foundin Mammalian Cell Biotechnology: a Practical Approach, M. Butler, ed.(IRL Press, 1991) and Sambrook et al., supra.

[3369] Methods of eukaryotic cell transfection and prokaryotic celltransformation are known to the ordinarily skilled artisan, for example,CaCl₂, CaPO₄, liposome-mediated and electroporation. Depending on thehost cell used, transformation is performed using standard techniquesappropriate to such cells. The calcium treatment employing calciumchloride, as described in Sambrook et al., supra, or electroporation isgenerally used for prokaryotes. Infection with Agrobacterium tumefaciensis used for transformation of certain plant cells, as described by Shawet al., Gene, 23:315 (1983) and WO 89/05859 published Jun. 29, 1989. Formammalian cells without such cell walls, the calcium phosphateprecipitation method of Graham and van der Eb, Virology, 52:456-457(1978) can be employed. General aspects of mammalian cell host systemtransfections have been described in U.S. Pat. No. 4,399,216.Transformations into yeast are typically carried out according to themethod of Van Solingen et al., J. Bact., 130:946 (1977) and Hsiao etal., Proc. Natl. Acad. Sci. (USA), 76:3829 (1979). However, othermethods for introducing DNA into cells, such as by nuclearmicroinjection, electroporation, bacterial protoplast fusion with intactcells, or polycations, e.g., polybrene, polyornithine, may also be used.For various techniques for transforming mammalian cells, see Keown etal., Methods in Enzymology, 185:527-537 (1990) and Mansour et al.,Nature, 336:348-352 (1988).

[3370] Suitable host cells for cloning or expressing the DNA in thevectors herein include prokaryote, yeast, or higher eukaryote cells.Suitable prokaryotes include but are not limited to eubacteria, such asGram-negative or Gram-positive organisms, for example,Enterobacteriaceae such as E. coli. Various E. coli strains are publiclyavailable, such as E. coli K12 strain MM294 (ATCC 31,446); E. coli X1776(ATCC 31,537); E. coli strain W3110 (ATCC 27,325) and K5 772 (ATCC53,635). Other suitable prokaryotic host cells includeEnterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter,Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium,Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacillisuch as B. subtilis and B. licheniformis (e.g., B. licheniformis 41Pdisclosed in DD 266,710 published Apr. 12, 1989), Pseudomonas such as P.aeruginosa, and Streptomyces. These examples are illustrative ratherthan limiting. Strain W3110 is one particularly preferred host or parenthost because it is a common host strain for recombinant DNA productfermentations. Preferably, the host cell secretes minimal amounts ofproteolytic enzymes. For example, strain W3110 may be modified to effecta genetic mutation in the genes encoding proteins endogenous to thehost, with examples of such hosts including E. coli W3110 strain 1A2,which has the complete genotype tonA; E. coli W3110 strain 9E4, whichhas the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC55,244), which has the complete genotype tonA ptr3 phoA E15(argF-lac)169 degP ompT kan^(r) ; E. coli W3110 strain 37D6, which hasthe complete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompTrbs7ilvG kan^(r) ; E. coli W3110 strain 40B4, which is strain 37D6 witha non-kanamycin resistant degP deletion mutation; and an E. coli strainhaving mutant periplasmic protease disclosed in U.S. Pat. No. 4,946,783issued Aug. 7, 1990. Alternatively, in vitro methods of cloning, e.g.,PCR or other nucleic acid polymerase reactions, are suitable.

[3371] In addition to prokaryotes, eukaryotic microbes such asfilamentous fungi or yeast are suitable cloning or expression hosts forPRO-encoding vectors. Saccharomyces cerevisiae is a commonly used lowereukaryotic host microorganism. Others include Schizosaccharomyces pombe(Beach and Nurse, Nature, 290: 140 [1981]; EP 139,383 published May 2,1985); Kluyveromyces hosts (U.S. Pat. No. 4,943,529; Fleer et al.,Bio/Technology, 9:968-975 (1991)) such as, e.g., K. lactis (MW98-8C,CBS683, CBS4574; Louvencourt et al., J. Bacteriol., 154(2):737-742[1983]), K. fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K.wickeramii (ATCC 24,178), K. waltii (ATCC 56,500), K. drosophilarum(ATCC 36,906; Van den Berg et al., Bio/Technology, 8:135 (1990)), K.thermotolerans, and K. marxianus; yarrowia (EP 402,226); Pichia pastoris(EP 183,070; Sreekrishna et al., J. Basic Microbiol., 28:265-278[1988]); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa(Case et al., Proc. Natl. Acad. Sci. USA, 76:5259-5263 [1979]);Schwanniomyces such as Schwanniomyces occidentalis (EP 394,538 publishedOct. 31, 1990); and filamentous fungi such as, e.g., Neurospora,Penicillium, Tolypocladium (WO 91/00357 published Jan. 10, 1991), andAspergillus hosts such as A. nidulans (Ballance et al., Biochem.Biophys. Res. Commun., 112:284-289 [1983]; Tilburn et al., Gene,26:205-221 [1983]; Yelton et al., Proc. Natl. Acad. Sci. USA, 81:1470-1474 [1984]) and A. niger (Kelly and Hynes, EMBO J., 4:475-479[1985]). Methylotropic yeasts are suitable herein and include, but arenot limited to, yeast capable of growth on methanol selected from thegenera consisting of Hansenula, Candida, Kloeckera, Pichia,Saccharomyces, Torulopsis, and Rhodotorula. A list of specific speciesthat are exemplary of this class of yeasts may be found in C. Anthony,The Biochemistry of Methylotrophs, 269 (1982).

[3372] Suitable host cells for the expression of glycosylated PRO arederived from multicellular organisms. Examples of invertebrate cellsinclude insect cells such as Drosophila S2 and Spodoptera Sf9, as wellas plant cells. Examples of useful mammalian host cell lines includeChinese hamster ovary (CHO) and COS cells. More specific examplesinclude monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL1651); human embryonic kidney line (293 or 293 cells subcloned forgrowth in suspension culture, Graham et al., J. Gen Virol., 36:59(1977)); Chinese hamster ovary cells/-DHFR (CHO, Urlaub and Chasin,Proc. Natl. Acad. Sci. USA, 77:4216 (1980)); mouse sertoli cells (TM4,Mather, Biol. Reprod., 23:243-251 (1980)); human lung cells (W138, ATCCCCL 75); human liver cells (Hep G2, HB 8065); and mouse mammary tumor(MMT 060562, ATCC CCL51). The selection of the appropriate host cell isdeemed to be within the skill in the art.

[3373] 3. Selection and Use of a Replicable Vector

[3374] The nucleic acid (e.g., cDNA or genomic DNA) encoding PRO may beinserted into a replicable vector for cloning (amplification of the DNA)or for expression. Various vectors are publicly available. The vectormay, for example, be in the form of a plasmid, cosmid, viral particle,or phage. The appropriate nucleic acid sequence may be inserted into thevector by a variety of procedures. In general, DNA is inserted into anappropriate restriction endonuclease site(s) using techniques known inthe art. Vector components generally include, but are not limited to,one or more of a signal sequence, an origin of replication, one or moremarker genes, an enhancer element, a promoter, and a transcriptiontermination sequence. Construction of suitable vectors containing one ormore of these components employs standard ligation techniques which areknown to the skilled artisan.

[3375] The PRO may be produced recombinantly not only directly, but alsoas a fusion polypeptide with a heterologous polypeptide, which may be asignal sequence or other polypeptide having a specific cleavage site atthe N-terminus of the mature protein or polypeptide. In general, thesignal sequence may be a component of the vector, or it may be a part ofthe PRO-encoding DNA that is inserted into the vector. The signalsequence may be a prokaryotic signal sequence selected, for example,from the group of the alkaline phosphatase, penicillinase, 1pp, orheat-stable enterotoxin II leaders. For yeast secretion the signalsequence may be, e.g., the yeast invertase leader, alpha factor leader(including Saccharomyces and Kluyveromyces α-factor leaders, the latterdescribed in U.S. Pat. No. 5,010,182), or acid phosphatase leader, theC. albicans glucoamylase leader (EP 362,179 published Apr. 4, 1990), orthe signal described in WO 90/13646 published Nov. 15, 1990. Inmammalian cell expression, mammalian signal sequences may be used todirect secretion of the protein, such as signal sequences from secretedpolypeptides of the same or related species, as well as viral secretoryleaders.

[3376] Both expression and cloning vectors contain a nucleic acidsequence that enables the vector to replicate in one or more selectedhost cells. Such sequences are well known for a variety of bacteria,yeast, and viruses. The origin of replication from the plasmid pBR322 issuitable for most Gram-negative bacteria, the 2μ plasmid origin issuitable for yeast, and various viral origins (SV40, polyoma,adenovirus, VSV or BPV) are useful for cloning vectors in mammaliancells.

[3377] Expression and cloning vectors will typically contain a selectiongene, also termed a selectable marker. Typical selection genes encodeproteins that (a) confer resistance to antibiotics or other toxins,e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b)complement auxotrophic deficiencies, or (c) supply critical nutrientsnot available from complex media, e.g., the gene encoding D-alanineracemase for Bacilli.

[3378] An example of suitable selectable markers for mammalian cells arethose that enable the identification of cells competent to take up thePRO-encoding nucleic acid, such as DHFR or thymidine kinase. Anappropriate host cell when wild-type DHFR is employed is the CHO cellline deficient in DHFR activity, prepared and propagated as described byUrlaub et al., Proc. Natl. Acad. Sci. USA, 77:4216 (1980). A suitableselection gene for use in yeast is the trp1 gene present in the yeastplasmid YRp7 [Stinchcomb et al., Nature, 282:39 (1979); Kingsman et al.,Gene, 7:141 (1979); Tschemper et al., Gene, 10:157 (1980)]. The trp1gene provides a selection marker for a mutant strain of yeast lackingthe ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1[Jones, Genetics, 85:12 (1977)].

[3379] Expression and cloning vectors usually contain a promoteroperably linked to the PRO-encoding nucleic acid sequence to direct mRNAsynthesis. Promoters recognized by a variety of potential host cells arewell known. Promoters suitable for use with prokaryotic hosts includethe β-lactamase and lactose promoter systems [Chang et al., Nature,275:615 (1978); Goeddel et al., Nature, 281:544 (1979)], alkalinephosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic AcidsRes., 8:4057 (1980); EP 36,776], and hybrid promoters such as the tacpromoter [deBoer et al., Proc. Natl. Acad. Sci. USA, 80:21-25 (1983)].Promoters for use in bacterial systems also will contain aShine-Dalgarno (S.D.) sequence operably linked to the DNA encoding PRO.

[3380] Examples of suitable promoting sequences for use with yeast hostsinclude the promoters for 3-phosphoglycerate kinase [Hitzeman et al., J.Biol. Chem., 255:2073 (1980)] or other glycolytic enzymes [Hess et al.,J. Adv. Enzyme Reg., 7:149 (1968); Holland, Biochemistry, 17:4900(1978)], such as enolase, glyceraldehyde-3-phosphate dehydrogenase,hexokinase, pyruvate decarboxylase, phosphofructokinase,glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvatekinase, triosephosphate isomerase, phosphoglucose isomerase, andglucokinase.

[3381] Other yeast promoters, which are inducible promoters having theadditional advantage of transcription controlled by growth conditions,are the promoter regions for alcohol dehydrogenase 2, isocytochrome C,acid phosphatase, degradative enzymes associated with nitrogenmetabolism, metallothionein, glyceraldehyde-3-phosphate dehydrogenase,and enzymes responsible for maltose and galactose utilization. Suitablevectors and promoters for use in yeast expression are further describedin EP 73,657.

[3382] PRO transcription from vectors in mammalian host cells iscontrolled, for example, by promoters obtained from the genomes ofviruses such as polyoma virus, fowlpox virus (UK 2,211,504 publishedJul. 5, 1989), adenovirus (such as Adenovirus 2), bovine papillomavirus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-Bvirus and Simian Virus 40 (SV40), from heterologous mammalian promoters,e.g., the actin promoter or an immunoglobulin promoter, and fromheat-shock promoters, provided such promoters are compatible with thehost cell systems.

[3383] Transcription of a DNA encoding the PRO by higher eukaryotes maybe increased by inserting an enhancer sequence into the vector.Enhancers are cis-acting elements of DNA, usually about from 10 to 300bp, that act on a promoter to increase its transcription. Many enhancersequences are now known from mammalian genes (globin, elastase, albumin,α-fetoprotein, and insulin). Typically, however, one will use anenhancer from a eukaryotic cell virus. Examples include the SV40enhancer on the late side of the replication origin (bp 100-270), thecytomegalovirus early promoter enhancer, the polyoma enhancer on thelate side of the replication origin, and adenovirus enhancers. Theenhancer may be spliced into the vector at a position 5′ or 3′ to thePRO coding sequence, but is preferably located at a site 5′ from thepromoter.

[3384] Expression vectors used in eukaryotic host cells (yeast, fungi,insect, plant, animal, human, or nucleated cells from othermulticellular organisms) will also contain sequences necessary for thetermination of transcription and for stabilizing the mRNA. Suchsequences are commonly available from the 5′ and, occasionally 3′,untranslated regions of eukaryotic or viral DNAs or cDNAs. These regionscontain nucleotide segments transcribed as polyadenylated fragments inthe untranslated portion of the mRNA encoding PRO.

[3385] Still other methods, vectors, and host cells suitable foradaptation to the synthesis of PRO in recombinant vertebrate cellculture are described in Gething et al., Nature, 293:620-625 (1981);Mantei et al., Nature, 281:4046 (1979); EP 117,060; and EP 117,058.

[3386] 4. Detecting Gene Amplification/Expression

[3387] Gene amplification and/or expression may be measured in a sampledirectly, for example, by conventional Southernblotting,Northernblotting to quantitate the transcriptionof mRNA [Thomas, Proc.Natl. Acad. Sci. USA, 77:5201-5205 (1980)], dot blotting (DNA analysis),or in situ hybridization, using an appropriately labeled probe, based onthe sequences provided herein. Alternatively, antibodies may be employedthat can recognize specific duplexes, including DNA duplexes, RNAduplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Theantibodies in turn may be labeled and the assay may be carried out wherethe duplex is bound to a surface, so that upon the formation of duplexon the surface, the presence of antibody bound to the duplex can bedetected.

[3388] Gene expression, alternatively, may be measured by immunologicalmethods, such as immunohistochemical staining of cells or tissuesections and assay of cell culture or body fluids, to quantitatedirectly the expression of gene product. Antibodies useful forimmunohistochemical staining and/or assay of sample fluids may be eithermonoclonal or polyclonal, and may be prepared in any mammal.Conveniently, the antibodies may be prepared against a native sequencePRO polypeptide or against a synthetic peptide based on the DNAsequences provided herein or against exogenous sequence fused to PRO DNAand encoding a specific antibody epitope.

[3389] 5. Purification of Polypeptide

[3390] Forms of PRO may be recovered from culture medium or from hostcell lysates. If membrane-bound, it can be released from the membraneusing a suitable detergent solution (e.g. Triton-X 100) or by enzymaticcleavage. Cells employed in expression of PRO can be disrupted byvarious physical or chemical means, such as freeze-thaw cycling,sonication, mechanical disruption, or cell lysing agents.

[3391] It may be desired to purify PRO from recombinant cell proteins orpolypeptides. The following procedures are exemplary of suitablepurification procedures: by fractionation on an ion-exchange column;ethanol precipitation; reverse phase HPLC; chromatography on silica oron a cation-exchange resin such as DEAE; chromatofocusing; SDS-PAGE;ammonium sulfate precipitation; gel filtration using, for example,Sephadex G-75; protein A Sepharose columns to remove contaminants suchas IgG; and metal chelating columns to bind epitope-tagged forms of thePRO. Various methods of protein purification may be employed and suchmethods are known in the art and described for example in Deutscher,Methods in Enzymology, 182 (1990); Scopes, Protein Purification:Principles and Practice, Springer-Verlag, New York (1982). Thepurification step(s) selected will depend, for example, on the nature ofthe production process used and the particular PRO produced.

[3392] E. Uses for PRO

[3393] Nucleotide sequences (or their complement) encoding PRO havevarious applications in the art of molecular biology, including uses ashybridization probes, in chromosome and gene mapping and in thegeneration of anti-sense RNA and DNA. PRO nucleic acid will also beuseful for the preparation of PRO polypeptides by the recombinanttechniques described herein.

[3394] The full-length native sequence PRO gene, or portions thereof,may be used as hybridization probes for a cDNA library to isolate thefull-length PRO cDNA or to isolate still other cDNAs (for instance,those encoding naturally-occurring variants of PRO or PRO from otherspecies) which have a desired sequence identity to the native PROsequence disclosed herein. Optionally, the length of the probes will beabout 20 to about 50 bases. The hybridization probes may be derived fromat least partially novel regions of the full length native nucleotidesequence wherein those regions may be determined without undueexperimentation or from genomic sequences including promoters, enhancerelements and introns of native sequence PRO. By way of example, ascreening method will comprise isolating the coding region of the PROgene using the known DNA sequence to synthesize a selected probe ofabout 40 bases. Hybridization probes may be labeled by a variety oflabels, including radionucleotides such as ³²P or ³⁵S, or enzymaticlabels such as alkaline phosphatase coupled to the probe viaavidintbiotin coupling systems. Labeled probes having a sequencecomplementary to that of the PRO gene of the present invention can beused to screen libraries of human cDNA, genomic DNA or mRNA to determinewhich members of such libraries the probe hybridizes to. Hybridizationtechniques are described in further detail in the Examples below.

[3395] Any EST sequences disclosed in the present application maysimilarly be employed as probes, using the methods disclosed herein.

[3396] Other useful fragments of the PRO nucleic acids include antisenseor sense oligonucleotides comprising a singe-stranded nucleic acidsequence (either RNA or DNA) capable of binding to target PRO mRNA(sense) or PRO DNA (antisense) sequences. Antisense or senseoligonucleotides, according to the present invention, comprise afragment of the coding region of PRO DNA. Such a fragment generallycomprises at least about 14 nucleotides, preferably from about 14 to 30nucleotides. The ability to derive an antisense or a senseoligonucleotide, based upon a cDNA sequence encoding a given protein isdescribed in, for example, Stein and Cohen (Cancer Res. 48:2659, 1988)and van der Krol et al. (BioTechniques 6:958, 1988).

[3397] Binding of antisense or sense oligonucleotides to target nucleicacid sequences results in the formation of duplexes that blocktranscription or translation of the target sequence by one of severalmeans, including enhanced degradation of the duplexes, prematuretermination of transcription or translation, or by other means. Theantisense oligonucleotides thus may be used to block expression of PROproteins. Antisense or sense oligonucleotides further compriseoligonucleotides having modified sugar-phosphodiester backbones (orother sugar linkages, such as those described in WO 91/06629) andwherein such sugar linkages are resistant to endogenous nucleases. Sucholigonucleotides with resistant sugar linkages are stable in vivo (i.e.,capable of resisting enzymatic degradation) but retain sequencespecificity to be able to bind to target nucleotide sequences.

[3398] Other examples of sense or antisense oligonucleotides includethose oligonucleotides which are covalently linked to organic moieties,such as those described in WO 90/10048, and other moieties thatincreases affinity of the oligonucleotide for a target nucleic acidsequence, such as poly-(L-lysine). Further still, intercalating agents,such as ellipticine, and alkylating agents or metal complexes may beattached to sense or antisense oligonucleotides to modify bindingspecificities of the antisense or sense oligonucleotide for the targetnucleotide sequence.

[3399] Antisense or sense oligonucleotides may be introduced into a cellcontaining the target nucleic acid sequence by any gene transfer method,including, for example, CaPO₄-mediated DNA transfection,electroporation, or by using gene transfer vectors such as Epstein-Barrvirus. In a preferred procedure, an antisense or sense oligonucleotideis inserted into a suitable retroviral vector. A cell containing thetarget nucleic acid sequence is contacted with the recombinantretroviral vector, either in vivo or ex vivo. Suitable retroviralvectors include, but are not limited to, those derived from the murineretrovirus M-MuLV, N2 (a retrovirus derived from M-MuLV), or the doublecopy vectors designated DCT5A, DCT5B and DCT5C (see WO 90/13641).

[3400] Sense or antisense oligonucleotides also may be introduced into acell containing the target nucleotide sequence by formation of aconjugate with a ligand binding molecule, as described in WO 91/04753.Suitable ligand binding molecules include, but are not limited to, cellsurface receptors, growth factors, other cytokines, or other ligandsthat bind to cell surface receptors. Preferably, conjugation of theligand binding molecule does not substantially interfere with theability of the ligand binding molecule to bind to its correspondingmolecule or receptor, or block entry of the sense or antisenseoligonucleotide or its conjugated version into the cell.

[3401] Alternatively, a sense or an antisense oligonucleotide may beintroduced into a cell containing the target nucleic acid sequence byformation of an oligonucleotide-lipid complex, as described in WO90/10448. The sense or antisense oligonucleotide-lipid complex ispreferably dissociated within the cell by an endogenous lipase.

[3402] Antisense or sense RNA or DNA molecules are generally at leastabout 5 bases in length, about 10 bases in length, about 15 bases inlength, about 20 bases in length, about 25 bases in length, about 30bases in length, about 35 bases in length, about 40 bases in length,about 45 bases in length, about 50 bases in length, about 55 bases inlength, about 60 bases in length, about 65 bases in length, about 70bases in length, about 75 bases in length, about 80 bases in length,about 85 bases in length, about 90 bases in length, about 95 bases inlength, about 100 bases in length, or more.

[3403] The probes may also be employed in PCR techniques to generate apool of sequences for identification of closely related PRO codingsequences.

[3404] Nucleotide sequences encoding a PRO can also be used to constructhybridization probes for mapping the gene which encodes that PRO and forthe genetic analysis of individuals with genetic disorders. Thenucleotide sequences provided herein may be mapped to a chromosome andspecific regions of a chromosome using known techniques, such as in situhybridization, linkage analysis against known chromosomal markers, andhybridization screening with libraries.

[3405] When the coding sequences for PRO encode a protein which binds toanother protein (example, where the PRO is a receptor), the PRO can beused in assays to identify the other proteins or molecules involved inthe binding interaction. By such methods, inhibitors of thereceptor/ligand binding interaction can be identified. Proteins involvedin such binding interactions can also be used to screen for peptide orsmall molecule inhibitors or agonists of the binding interaction. Also,the receptor PRO can be used to isolate correlative ligand(s). Screeningassays can be designed to find lead compounds that mimic the biologicalactivity of a native PRO or a receptor for PRO. Such screening assayswill include assays amenable to high-throughput screening of chemicallibraries, making them particularly suitable for identifying smallmolecule drug candidates. Small molecules contemplated include syntheticorganic or inorganic compounds. The assays can be performed in a varietyof formats, including protein-protein binding assays, biochemicalscreening assays, immunoassays and cell based assays, which are wellcharacterized in the art.

[3406] Nucleic acids which encode PRO or its modified forms can also beused to generate either transgenic animals or “knock out” animals which,in turn, are useful in the development and screening of therapeuticallyuseful reagents. A transgenic animal (e.g., a mouse or rat) is an animalhaving cells that contain a transgene, which transgene was introducedinto the animal or an ancestor of the animal at a prenatal, e.g., anembryonic stage. A transgene is a DNA which is integrated into thegenome of a cell from which a transgenic animal develops. In oneembodiment, cDNA encoding PRO can be used to clone genomic DNA encodingPRO in accordance with established techniques and the genomic sequencesused to generate transgenic animals that contain cells which express DNAencoding PRO. Methods for generating transgenic animals, particularlyanimals such as mice or rats, have become conventional in the art andare described, for example, in U.S. Pat. Nos. 4,736,866 and 4,870,009.Typically, particular cells would be targeted for PRO transgeneincorporation with tissue-specific enhancers. Transgenic animals thatinclude a copy of a transgene encoding PRO introduced into the germ lineof the animal at an embryonic stage can be used to examine the effect ofincreased expression of DNA encoding PRO. Such animals can be used astester animals for reagents thought to confer protection from, forexample, pathological conditions associated with its overexpression. Inaccordance with this facet of the invention, an animal is treated withthe reagent and a reduced incidence of the pathological condition,compared to untreated animals bearing the transgene, would indicate apotential therapeutic intervention for the pathological condition.

[3407] Alternatively, non-human homologues of PRO can be used toconstruct a PRO “knock out” animal which has a defective or altered geneencoding PRO as a result of homologous recombination between theendogenous gene encoding PRO and altered genomic DNA encoding PROintroduced into an embryonic stem cell of the animal. For example, cDNAencoding PRO can be used to clone genomic DNA encoding PRO in accordancewith established techniques. A portion of the genomic DNA encoding PROcan be deleted or replaced with another gene, such as a gene encoding aselectable marker which can be used to monitor integration. Typically,several kilobases of unaltered flanking DNA (both at the 5′ and 3′ ends)are included in the vector [see e.g., Thomas and Capecchi, Cell, 51:503(1987) for a description of homologous recombination vectors]. Thevector is introduced into an embryonic stem cell line (e.g., byelectroporation) and cells in which the introduced DNA has homologouslyrecombined with the endogenous DNA are selected [see e.g., Li et al.,Cell, 69:915 (1992)]. The selected cells are then injected into ablastocyst of an animal (e.g., a mouse or rat) to form aggregationchimeras [see e.g., Bradley, in Teratocarcinomas and Embryonic StemCells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987),pp. 113-152]. A chimeric embryo can then be implanted into a suitablepseudopregnant female foster animal and the embryo brought to term tocreate a “knock out” animal. Progeny harboring the homologouslyrecombined DNA in their germ cells can be identified by standardtechniques and used to breed animals in which all cells of the animalcontain the homologously recombined DNA. Knockout animals can becharacterized for instance, for their ability to defend against certainpathological conditions and for their development of pathologicalconditions due to absence of the PRO polypeptide.

[3408] Nucleic acid encoding the PRO polypeptides may also be used ingene therapy. In gene therapy applications, genes are introduced intocells in order to achieve in vivo synthesis of a therapeuticallyeffective genetic product, for example for replacement of a defectivegene. “Gene therapy” includes both conventional gene therapy where alasting effect is achieved by a single treatment, and the administrationof gene therapeutic agents, which involves the one time or repeatedadministration of a therapeutically effective DNA or mRNA. AntisenseRNAs and DNAs can be used as therapeutic agents for blocking theexpression of certain genes in vivo. It has already been shown thatshort antisense oligonucleotides can be imported into cells where theyact as inhibitors, despite their low intracellular concentrations causedby their restricted uptake by the cell membrane. (Zamecnik et al., Proc.Natl. Acad. Sci. USA 83:4143-4146 [1986]). The oligonucleotides can bemodified to enhance their uptake, e.g. by substituting their negativelycharged phosphodiester groups by uncharged groups.

[3409] There are a variety of techniques available for introducingnucleic acids into viable cells. The techniques vary depending uponwhether the nucleic acid is transferred into cultured cells in vitro, orin vivo in the cells of the intended host. Techniques suitable for thetransfer of nucleic acid into mammalian cells in vitro include the useof liposomes, electroporation, microinjection, cell fusion,DEAE-dextran, the calcium phosphate precipitation method, etc. Thecurrently preferred in vivo gene transfer techniques includetransfection with viral (typically retroviral) vectors and viral coatprotein-liposome mediated transfection (Dzau et al., Trends inBiotechnology 11, 205-210 [1993]). In some situations it is desirable toprovide the nucleic acid source with an agent that targets the targetcells, such as an antibody specific for a cell surface membrane proteinor the target cell, a ligand for a receptor on the target cell, etc.Where liposomes are employed, proteins which bind to a cell surfacemembrane protein associated with endocytosis may be used for targetingand/or to facilitate uptake, e.g. capsid proteins or fragments thereoftropic for a particular cell type, antibodies for proteins which undergointernalization in cycling, proteins that target intracellularlocalization and enhance intracellular half-life. The technique ofreceptor-mediated endocytosis is described, for example, by Wu et al.,J. Biol. Chem. 262, 44294432 (1987); and Wagner et al., Proc. Natl.Acad. Sci. USA 87, 3410-3414 (1990). For review of gene marking and genetherapy protocols see Anderson et al., Science 256, 808-813 (1992).

[3410] The PRO polypeptides described herein may also be employed asmolecular weight markers for protein electrophoresis purposes and theisolated nucleic acid sequences may be used for recombinantly expressingthose markers.

[3411] The nucleic acid molecules encoding the PRO polypeptides orfragments thereof described herein are useful for chromosomeidentification. In this regard, there exists an ongoing need to identifynew chromosome markers, since relatively few chromosome markingreagents, based upon actual sequence data are presently available. EachPRO nucleic acid molecule of the present invention can be used as achromosome marker.

[3412] The PRO polypeptides and nucleic acid molecules of the presentinvention may also be used for tissue typing, wherein the PROpolypeptides of the present invention may be differentially expressed inone tissue as compared to another. PRO nucleic acid molecules will finduse for generating probes for PCR, Northern analysis, Southern analysisand Western analysis.

[3413] The PRO polypeptides described herein may also be employed astherapeutic agents. The PRO polypeptides of the present invention can beformulated according to known methods to prepare pharmaceutically usefulcompositions, whereby the PRO product hereof is combined in admixturewith a pharmaceutically acceptable carrier vehicle. Therapeuticformulations are prepared for storage by mixing the active ingredienthaving the desired degree of purity with optional physiologicallyacceptable carriers, excipients or stabilizers (Remington'sPharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the formof lyophilized formulations or aqueous solutions. Acceptable carriers,excipients or stabilizers are nontoxic to recipients at the dosages andconcentrations employed, and include buffers such as phosphate, citrateand other organic acids; antioxidants including ascorbic acid; lowmolecular weight (less than about 10 residues) polypeptides; proteins,such as serum albumin, gelatin or immunoglobulins; hydrophilic polymerssuch as polyvinylpyrrolidone, amino acids such as glycine, glutamine,asparagine, arginine or lysine; monosaccharides, disaccharides and othercarbohydrates including glucose, mannose, or dextrins; chelating agentssuch as EDTA; sugar alcohols such as mannitol or sorbitol; salt-formingcounterions such as sodium; and/or nonionic surfactants such as TWEEN™,PLURONICS™ or PEG.

[3414] The formulations to be used for in vivo administration must besterile. This is readily accomplished by filtration through sterilefiltration membranes, prior to or following lyophilization andreconstitution.

[3415] Therapeutic compositions herein generally are placed into acontainer having a sterile access port, for example, an intravenoussolution bag or vial having a stopper pierceable by a hypodermicinjection needle.

[3416] The route of administration is in accord with known methods, e.g.injection or infusion by intravenous, intraperitoneal, intracerebral,intramuscular, intraocular, intraarterial or intralesional routes,topical administration, or by sustained release systems.

[3417] Dosages and desired drug concentrations of pharmaceuticalcompositions of the present invention may vary depending on theparticular use envisioned. The determination of the appropriate dosageor route of administration is well within the skill of an ordinaryphysician. Animal experiments provide reliable guidance for thedetermination of effective doses for human therapy. Interspecies scalingof effective doses can be performed following the principles laid downby Mordenti, J. and Chappell, W. “The use of interspecies scaling intoxicolinetics” In Toxicokinetics and New Drug Development, Yacobi etal., Eds., Pergamon Press, New York 1989, pp. 42-96.

[3418] When in vivo administration of a PRO polypeptide or agonist orantagonist thereof is employed, normal dosage amounts may vary fromabout 10 ng/kg to up to 100 mg/kg of mammal body weight or more per day,preferably about 1 μg/kg/day to 10 mg/kg/day, depending upon the routeof administration. Guidance as to particular dosages and methods ofdelivery is provided in the literature; see, for example, U.S. Pat. Nos.4,657,760; 5,206,344; or 5,225,212. It is anticipated that differentformulations will be effective for different treatment compounds anddifferent disorders, that administration targeting one organ or tissue,for example, may necessitate delivery in a manner different from that toanother organ or tissue.

[3419] Where sustained-release administration of a PRO polypeptide isdesired in a formulation with release characteristics suitable for thetreatment of any disease or disorder requiring administration of the PROpolypeptide, microencapsulation of the PRO polypeptide is contemplated.Microencapsulation of recombinant proteins for sustained release hasbeen successfully performed with human growth hormone (rhGH),interferon-(rhIFN-), interleukin-2, and MN rgp120. Johnson et al., Nat.Med., 2:795-799 (1996); Yasuda, Biomed. Ther., 27:1221-1223 (1993); Horaet al., Bio/Technology. 8:755-758(1990); Cleland, “Design and Productionof Single Immunization Vaccines Using Polylactide PolyglycolideMicrosphere Systems,” in Vaccine Design: The Subunit and AdjuvantApproach, Powell and Newman, eds, (Plenum Press: New York, 1995), pp.439-462; WO 97/03692, WO 96/40072, WO 96/07399; and U.S. Pat. No.5,654,010.

[3420] The sustained-release formulations of these proteins weredeveloped using poly-lactic-coglycolic acid (PLGA) polymer due to itsbiocompatibility and wide range of biodegradable properties. Thedegradation products of PLGA, lactic and glycolic acids, can be clearedquickly within the human body. Moreover, the degradability of thispolymer can be adjusted from months to years depending on its molecularweight and composition. Lewis, “Controlled release of bioactive agentsfrom lactide/glycolide polymer,” in: M. Chasin and R. Langer (Eds.),Biodegradable Polymers as Drug Delivery Systems (Marcel Dekker: NewYork, 1990), pp. 1-41.

[3421] This invention encompasses methods of screening compounds toidentify those that mimic the PRO polypeptide (agonists) or prevent theeffect of the PRO polypeptide (antagonists). Screening assays forantagonist drug candidates are designed to identify compounds that bindor complex with the PRO polypeptides encoded by the genes identifiedherein, or otherwise interfere with the interaction of the encodedpolypeptides with other cellular proteins. Such screening assays willinclude assays amenable to high-throughput screening of chemicallibraries, making them particularly suitable for identifying smallmolecule drug candidates.

[3422] The assays can be performed in a variety of formats, includingprotein-protein binding assays, biochemical screening assays,immunoassays, and cell-based assays, which are well characterized in theart.

[3423] All assays for antagonists are common in that they call forcontacting the drug candidate with a PRO polypeptide encoded by anucleic acid identified herein under conditions and for a timesufficient to allow these two components to interact.

[3424] In binding assays, the interaction is binding and the complexformed can be isolated or detected in the reaction mixture. In aparticular embodiment, the PRO polypeptide encoded by the geneidentified herein or the drug candidate is immobilized on a solid phase,e.g., on a microtiter plate, by covalent or non-covalent attachments.Non-covalent attachment generally is accomplished by coating the solidsurface with a solution of the PRO polypeptide and drying.Alternatively, an immobilized antibody, e.g., a monoclonal antibody,specific for the PRO polypeptide to be immobilized can be used to anchorit to a solid surface. The assay is performed by adding thenon-immobilized component, which may be labeled by a detectable label,to the immobilized component, e.g., the coated surface containing theanchored component. When the reaction is complete, the non-reactedcomponents are removed, e.g., by washing, and complexes anchored on thesolid surface are detected. When the originally non-immobilizedcomponent carries a detectable label, the detection of label immobilizedon the surface indicates that complexing occurred. Where the originallynon-immobilized component does not carry a label, complexing can bedetected, for example, by using a labeled antibody specifically bindingthe immobilized complex.

[3425] If the candidate compound interacts with but does not bind to aparticular PRO polypeptide encoded by a gene identified herein, itsinteraction with that polypeptide can be assayed by methods well knownfor detecting protein-protein interactions. Such assays includetraditional approaches, such as, e.g., cross-linking,co-immunoprecipitation, and co-purification through gradients orchromatographic columns. In addition, protein-protein interactions canbe monitored by using a yeast-based genetic system described by Fieldsand co-workers (Fields and Song, Nature (London), 340:245-246 (1989);Chien et al., Proc. Natl. Acad. Sci. USA, 88:9578-9582 (1991)) asdisclosed by Chevray and Nathans, Proc. Natl. Acad. Sci. USA, 89:5789-5793 (1991). Many transcriptional activators, such as yeast GAL4,consist of two physically discrete modular domains, one acting as theDNA-binding domain, the other one functioning as thetranscription-activation domain. The yeast expression system describedin the foregoing publications (generally referred to as the “two-hybridsystem”) takes advantage of this property, and employs two hybridproteins, one in which the target protein is fused to the DNA-bindingdomain of GAL4, and another, in which candidate activating proteins arefused to the activation domain. The expression of a GAL1-lacZ reportergene under control of a GAL4-activated promoter depends onreconstitution of GAL4 activity via protein-protein interaction.Colonies containing interacting polypeptides are detected with achromogenic substrate for β-galactosidase. A complete kit (MATCHMAKER™)for identifying protein-protein interactions between two specificproteins using the two-hybrid technique is commercially available fromClontech. This system can also be extended to map protein domainsinvolved in specific protein interactions as well as to pinpoint aminoacid residues that are crucial for these interactions.

[3426] Compounds that interfere with the interaction of a gene encodinga PRO polypeptide identified herein and other intra- or extracellularcomponents can be tested as follows: usually a reaction mixture isprepared containing the product of the gene and the intra- orextracellular component under conditions and for a time allowing for theinteraction and binding of the two products. To test the ability of acandidate compound to inhibit binding, the reaction is run in theabsence and in the presence of the test compound. In addition, a placebomay be added to a third reaction mixture, to serve as positive control.The binding (complex formation) between the test compound and the intra-or extracellular component present in the mixture is monitored asdescribed hereinabove. The formation of a complex in the controlreaction(s) but not in the reaction mixture containing the test compoundindicates that the test compound interferes with the interaction of thetest compound and its reaction partner.

[3427] To assay for antagonists, the PRO polypeptide may be added to acell along with the compound to be screened for a particular activityand the ability of the compound to inhibit the activity of interest inthe presence of the PRO polypeptide indicates that the compound is anantagonist to the PRO polypeptide. Alternatively, antagonists may bedetected by combining the PRO polypeptide and a potential antagonistwith membrane-bound PRO polypeptide receptors or recombinant receptorsunder appropriate conditions for a competitive inhibition assay. The PROpolypeptide can be labeled, such as by radioactivity, such that thenumber of PRO polypeptide molecules bound to the receptor can be used todetermine the effectiveness of the potential antagonist. The geneencoding the receptor can be identified by numerous methods known tothose of skill in the art, for example, ligand panning and FACS sorting.Coligan et al., Current Protocols in Immun., 1(2): Chapter 5 (1991).Preferably, expression cloning is employed wherein polyadenylated RNA isprepared from a cell responsive to the PRO polypeptide and a cDNAlibrary created from this RNA is divided into pools and used totransfect COS cells or other cells that are not responsive to the PROpolypeptide. Transfected cells that are grown on glass slides areexposed to labeled PRO polypeptide. The PRO polypeptide can be labeledby a variety of means including iodination or inclusion of a recognitionsite for a site-specific protein kinase. Following fixation andincubation, the slides are subjected to autoradiographic analysis.Positive pools are identified and sub-pools are prepared andre-transfected using an interactive sub-pooling and re-screeningprocess, eventually yielding a single clone that encodes the putativereceptor.

[3428] As an alternative approach for receptor identification, labeledPRO polypeptide can be photoaffinity-linked with cell membrane orextract preparations that express the receptor molecule. Cross-linkedmaterial is resolved by PAGE and exposed to X-ray film. The labeledcomplex containing the receptor can be excised, resolved into peptidefragments, and subjected to protein micro-sequencing. The amino acidsequence obtained from micro-sequencing would be used to design a set ofdegenerate oligonucleotide probes to screen a cDNA library to identifythe gene encoding the putative receptor.

[3429] In another assay for antagonists, mammalian cells or a membranepreparation expressing the receptor would be incubated with labeled PROpolypeptide in the presence of the candidate compound. The ability ofthe compound to enhance or block this interaction could then bemeasured.

[3430] More specific examples of potential antagonists include anoligonucleotide that binds to the fusions of immunoglobulin with PROpolypeptide, and, in particular, antibodies including, withoutlimitation, poly- and monoclonal antibodies and antibody fragments,single-chain antibodies, anti-idiotypic antibodies, and chimeric orhumanized versions of such antibodies or fragments, as well as humanantibodies and antibody fragments. Alternatively, a potential antagonistmay be a closely related protein, for example, a mutated form of the PROpolypeptide that recognizes the receptor but imparts no effect, therebycompetitively inhibiting the action of the PRO polypeptide.

[3431] Another potential PRO polypeptide antagonist is an antisense RNAor DNA construct prepared using antisense technology, where, e.g., anantisense RNA or DNA molecule acts to block directly the translation ofmRNA by hybridizing to targeted mRNA and preventing protein translation.Antisense technology can be used to control gene expression throughtriple-helix formation or antisense DNA or RNA, both of which methodsare based on binding of a polynucleotide to DNA or RNA. For example, the5′ coding portion of the polynucleotide sequence, which encodes themature PRO polypeptides herein, is used to design an antisense RNAoligonucleotide of from about 10 to 40 base pairs in length. A DNAoligonucleotide is designed to be complementary to a region of the geneinvolved in transcription (triple helix—see Lee et al., Nucl. AcidsRes., 6:3073 (1979); Cooney et al., Science, 241: 456 (1988); Dervan etal., Science, 251:1360 (1991)), thereby preventing transcription and theproduction of the PRO polypeptide. The antisense RNA oligonucleotidehybridizes to the mRNA in vivo and blocks translation of the mRNAmolecule into the PRO polypeptide (antisense—Okano, Neurochem., 56:560(1991); Oligodeoxnucleotides as Antisense Inhibitors of Gene Expression(CRC Press: Boca Raton, Fla., 1988). The oligonucleotides describedabove can also be delivered to cells such that the antisense RNA or DNAmay be expressed in vivo to inhibit production of the PRO polypeptide.When antisense DNA is used, oligodeoxyribonucleotides derived from thetranslation-initiation site, e.g., between about −10 and +10 positionsof the target gene nucleotide sequence, are preferred.

[3432] Potential antagonists include small molecules that bind to theactive site, the receptor binding site, or growth factor or otherrelevant binding site of the PRO polypeptide, thereby blocking thenormal biological activity of the PRO polypeptide. Examples of smallmolecules include, but are not limited to, small peptides orpeptide-like molecules, preferably soluble peptides, and syntheticnon-peptidyl organic or inorganic compounds.

[3433] Ribozymes are enzymatic RNA molecules capable of catalyzing thespecific cleavage of RNA. Ribozymes act by sequence-specifichybridization to the complementary target RNA, followed byendonucleolytic cleavage. Specific ribozyme cleavage sites within apotential RNA target can be identified by known techniques. For furtherdetails see, e.g., Rossi, Current Biology, 4:469-471 (1994), and PCTpublication No. WO 97/33551 (published Sep. 18, 1997).

[3434] Nucleic acid molecules in triple-helix formation used to inhibittranscription should be single-stranded and composed ofdeoxynucleotides. The base composition of these oligonucleotides isdesigned such that it promotes triple-helix formation via Hoogsteenbase-pairing rules, which generally require sizeable stretches ofpurines or pyrimidines on one strand of a duplex. For further detailssee, e.g., PCT publication No. WO 97/33551, supra.

[3435] These small molecules can be identified by any one or more of thescreening assays discussed hereinabove and/or by any other screeningtechniques well known for those skilled in the art.

[3436] Uses of the herein disclosed molecules may also be based upon thepositive functional assay hits disclosed and described below.

[3437] F. Anti-PRO Antibodies

[3438] The present invention further provides anti-PRO antibodies.Exemplary antibodies include polyclonal, monoclonal, humanized,bispecific, and heteroconjugate antibodies.

[3439] 1. Polyclonal Antibodies

[3440] The anti-PRO antibodies may comprise polyclonal antibodies.Methods of preparing polyclonal antibodies are known to the skilledartisan. Polyclonal antibodies can be raised in a mammal, for example,by one or more injections of an immunizing agent and, if desired, anadjuvant. Typically, the immunizing agent and/or adjuvant will beinjected in the mammal by multiple subcutaneous or intraperitonealinjections. The immunizing agent may include the PRO polypeptide or afusion protein thereof. It may be useful to conjugate the immunizingagent to a protein known to be immunogenic in the mammal beingimmunized. Examples of such immunogenic proteins include but are notlimited to keyhole limpet hemocyanin, serum albumin, bovinethyroglobulin, and soybean trypsin inhibitor. Examples of adjuvantswhich may be employed include Freund's complete adjuvant and MPL-TDMadjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).The immunization protocol may be selected by one skilled in the artwithout undue experimentation.

[3441] 2. Monoclonal Antibodies

[3442] The anti-PRO antibodies may, alternatively, be monoclonalantibodies. Monoclonal antibodies may be prepared using hybridomamethods, such as those described by Kohler and Milstein, Nature, 256:495(1975). In a hybridoma method, a mouse, hamster, or other appropriatehost animal, is typically immunized with an immunizing agent to elicitlymphocytes that produce or are capable of producing antibodies thatwill specifically bind to the immunizing agent. Alternatively, thelymphocytes may be immunized in vitro.

[3443] The immunizing agent will typically include the PRO polypeptideor a fusion protein thereof. Generally, either peripheral bloodlymphocytes (“PBLs”) are used if cells of human origin are desired, orspleen cells or lymph node cells are used if non-human mammalian sourcesare desired. The lymphocytes are then fused with an immortalized cellline using a suitable fusing agent, such as polyethylene glycol, to forma hybridoma cell [Goding, Monoclonal Antibodies: Principles andPractice, Academic Press, (1986) pp. 59-103]. Immortalized cell linesare usually transformed mammalian cells, particularly myeloma cells ofrodent, bovine and human origin. Usually, rat or mouse myeloma celllines are employed. The hybridoma cells may be cultured in a suitableculture medium that preferably contains one or more substances thatinhibit the growth or survival of the unfused, immortalized cells. Forexample, if the parental cells lack the enzyme hypoxanthine guaninephosphoribosyl transferase (HGPRT or HPRT), the culture medium for thehybridomas typically will include hypoxanthine, aminopterin, andthymidine (“HAT medium”), which substances prevent the growth ofHGPRT-deficient cells.

[3444] Preferred immortalized cell lines are those that fuseefficiently, support stable high level expression of antibody by theselected antibody-producing cells, and are sensitive to a medium such asHAT medium. More preferred immortalized cell lines are murine myelomalines, which can be obtained, for instance, from the Salk Institute CellDistribution Center, San Diego, Calif. and the American Type CultureCollection, Manassas, Va. Human myeloma and mouse-human heteromyelomacell lines also have been described for the production of humanmonoclonal antibodies [Kozbor, J. Immunol., 133:3001 (1984); Brodeur etal., Monoclonal Antibody Production Techniques and Applications, MarcelDekker, Inc., New York, (1987) pp. 51-63].

[3445] The culture medium in which the hybridoma cells are cultured canthen be assayed for the presence of monoclonal antibodies directedagainst PRO. Preferably, the binding specificity of monoclonalantibodies produced by the hybridoma cells is determined byimmunoprecipitation or by an in vitro binding assay, such asradioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).Such techniques and assays are known in the art. The binding affinity ofthe monoclonal antibody can, for example, be determined by the Scatchardanalysis of Munson and Pollard, Anal. Biochem., 107:220 (1980).

[3446] After the desired hybridoma cells are identified, the clones maybe subcloned by limiting dilution procedures and grown by standardmethods [Goding, supra]. Suitable culture media for this purposeinclude, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640medium. Alternatively, the hybridoma cells may be grown in vivo asascites in a mammal.

[3447] The monoclonal antibodies secreted by the subclones may beisolated or purified from the culture medium or ascites fluid byconventional immunoglobulin purification procedures such as, forexample, protein A-Sepharose, hydroxylapatite chromatography, gelelectrophoresis, dialysis, or affinity chromatography.

[3448] The monoclonal antibodies may also be made by recombinant DNAmethods, such as those described in U.S. Pat. No. 4,816,567. DNAencoding the monoclonal antibodies of the invention can be readilyisolated and sequenced using conventional procedures (e.g., by usingoligonucleotide probes that are capable of binding specifically to genesencoding the heavy and light chains of murine antibodies). The hybridomacells of the invention serve as a preferred source of such DNA. Onceisolated, the DNA may be placed into expression vectors, which are thentransfected into host cells such as simian COS cells, Chinese hamsterovary (CHO) cells, or myeloma cells that do not otherwise produceimmunoglobulin protein, to obtain the synthesis of monoclonal antibodiesin the recombinant host cells. The DNA also may be modified, forexample, by substituting the coding sequence for human heavy and lightchain constant domains in place of the homologous murine sequences [U.S.Pat. No. 4,816,567; Morrison et al., supra] or by covalently joining tothe immunoglobulin coding sequence all or part of the coding sequencefor a non-immunoglobulin polypeptide. Such a non-immunoglobulinpolypeptide can be substituted for the constant domains of an antibodyof the invention, or can be substituted for the variable domains of oneantigen-combining site of an antibody of the invention to create achimeric bivalent antibody.

[3449] The antibodies may be monovalent antibodies. Methods forpreparing monovalent antibodies are well known in the art. For example,one method involves recombinant expression of immunoglobulin light chainand modified heavy chain. The heavy chain is truncated generally at anypoint in the Fc region so as to prevent heavy chain crosslinking.Alternatively, the relevant cysteine residues are substituted withanother amino acid residue or are deleted so as to prevent crosslinking.

[3450] In vitro methods are also suitable for preparing monovalentantibodies. Digestion of antibodies to produce fragments thereof,particularly, Fab fragments, can be accomplished using routinetechniques known in the art.

[3451] 3. Human and Humanized Antibodies

[3452] The anti-PRO antibodies of the invention may further comprisehumanized antibodies or human antibodies. Humanized forms of non-human(e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulinchains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)₂ or otherantigen-binding subsequences of antibodies) which contain minimalsequence derived from non-human immunoglobulin. Humanized antibodiesinclude human immunoglobulins (recipient antibody) in which residuesfrom a complementary determining region (CDR) of the recipient arereplaced by residues from a CDR of a non-human species (donor antibody)such as mouse, rat or rabbit having the desired specificity, affinityand capacity. In some instances, Fv framework residues of the humanimmunoglobulin are replaced by corresponding non-human residues.Humanized antibodies may also comprise residues which are found neitherin the recipient antibody nor in the imported CDR or frameworksequences. In general, the humanized antibody will comprisesubstantially all of at least one, and typically two, variable domains,in which all or substantially all of the CDR regions correspond to thoseof a non-human immunoglobulin and all or substantially all of the FRregions are those of a human immunoglobulin consensus sequence. Thehumanized antibody optimally also will comprise at least a portion of animmunoglobulin constant region (Fc), typically that of a humanimmunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann etal., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol.,2:593-596 (1992)].

[3453] Methods for humanizing non-human antibodies are well known in theart. Generally, a humanized antibody has one or more amino acid residuesintroduced into it from a source which is non-human. These non-humanamino acid residues are often referred to as “import” residues, whichare typically taken from an “import” variable domain. Humanization canbe essentially performed following the method of Winter and co-workers[Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature,332:323-327 (1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)],by substituting rodent CDRs or CDR sequences for the correspondingsequences of a human antibody. Accordingly, such “humanized” antibodiesare chimeric antibodies (U.S. Pat. No. 4,816,567), wherein substantiallyless than an intact human variable domain has been substituted by thecorresponding sequence from a non-human species. In practice, humanizedantibodies are typically human antibodies in which some CDR residues andpossibly some FR residues are substituted by residues from analogoussites in rodent antibodies.

[3454] Human antibodies can also be produced using various techniquesknown in the art, including phage display libraries [Hoogenboom andWinter, J. Mol. Biol., 227;381 (1991); Marks et al., J. Mol. Biol.,222:581 (1991)]. The techniques of Cole et al. and Boerner et al. arealso available for the preparation of human monoclonal antibodies (Coleet al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77(1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991)]. Similarly,human antibodies can be made by introducing of human immunoglobulin lociinto transgenic animals, e.g., mice in which the endogenousimmunoglobulin genes have been partially or completely inactivated. Uponchallenge, human antibody production is observed, which closelyresembles that seen in humans in all respects, including generearrangement, assembly, and antibody repertoire. This approach isdescribed, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806;5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the followingscientific publications: Marks et al., Bio/Technology 10, 779-783(1992); Lonberg et al., Nature 368 856-859 (1994); Morrison, Nature 368,812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51 (1996);Neuberger, Nature Biotechnology 14, 826 (1996); Lonberg and Huszar,Intern. Rev. Immunol. 13 65-93 (1995).

[3455] 4. Bispecific Antibodies

[3456] Bispecific antibodies are monoclonal, preferably human orhumanized, antibodies that have binding specificities for at least twodifferent antigens. In the present case, one of the bindingspecificities is for the PRO, the other one is for any other antigen,and preferably for a cell-surface protein or receptor or receptorsubunit.

[3457] Methods for making bispecific antibodies are known in the art.Traditionally, the recombinant production of bispecific antibodies isbased on the co-expression of two immunoglobulin heavy-chain/light-chainpairs, where the two heavy chains have different specificities [Milsteinand Cuello, Nature, 305:537-539 (1983)]. Because of the randomassortment of immunoglobulin heavy and light chains, these hybridomas(quadromas) produce a potential mixture of ten different antibodymolecules, of which only one has the correct bispecific structure. Thepurification of the correct molecule is usually accomplished by affinitychromatography steps. Similar procedures are disclosed in WO 93/08829,published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659(1991).

[3458] Antibody variable domains with the desired binding specificities(antibody-antigen combining sites) can be fused to immunoglobulinconstant domain sequences. The fusion preferably is with animmunoglobulin heavy-chain constant domain, comprising at least part ofthe hinge, CH2, and CH3 regions. It is preferred to have the firstheavy-chain constant region (CH1) containing the site necessary forlight-chain binding present in at least one of the fusions. DNAsencoding the immunoglobulin heavy-chain fusions and, if desired, theimmunoglobulin light chain, are inserted into separate expressionvectors, and are co-transfected into a suitable host organism. Forfurther details of generating bispecific antibodies see, for example,Suresh et al., Methods in Enzymology, 121:210 (1986).

[3459] According to another approach described in WO 96/27011, theinterface between a pair of antibody molecules can be engineered tomaximize the percentage of heterodimers which are recovered fromrecombinant cell culture. The preferred interface comprises at least apart of the CH3 region of an antibody constant domain. In this method,one or more small amino acid side chains from the interface of the firstantibody molecule are replaced with larger side chains (e.g. tyrosine ortryptophan). Compensatory “cavities” of identical or similar size to thelarge side chain(s) are created on the interface of the second antibodymolecule by replacing large amino acid side chains with smaller ones(e.g. alanine or threonine). This provides a mechanism for increasingthe yield of the heterodimer over other unwanted end-products such ashomodimers.

[3460] Bispecific antibodies can be prepared as full length antibodiesor antibody fragments (e.g. F(ab′)₂ bispecific antibodies). Techniquesfor generating bispecific antibodies from antibody fragments have beendescribed in the literature. For example, bispecific antibodies can beprepared can be prepared using chemical linkage. Brennan et al., Science229:81 (1985) describe a procedure wherein intact antibodies areproteolytically cleaved to generate F(ab′)₂ fragments. These fragmentsare reduced in the presence of the dithiol complexing agent sodiumarsenite to stabilize vicinal dithiols and prevent intermoleculardisulfide formation. The Fab′ fragments generated are then converted tothionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives isthen reconverted to the Fab′-thiol by reduction with mercaptoethylamineand is mixed with an equimolar amount of the other Fab′-TNB derivativeto form the bispecific antibody. The bispecific antibodies produced canbe used as agents for the selective immobilization of enzymes.

[3461] Fab′ fragments may be directly recovered from E. coli andchemically coupled to form bispecific antibodies. Shalaby et al., J.Exp. Med. 175:217-225 (1992) describe the production of a fullyhumanized bispecific antibody F(ab′)₂ molecule. Each Fab′ fragment wasseparately secreted from E. coli and subjected to directed chemicalcoupling in vitro to form the bispecific antibody. The bispecificantibody thus formed was able to bind to cells overexpressing the ErbB2receptor and normal human T cells, as well as trigger the lytic activityof human cytotoxic lymphocytes against human breast tumor targets.

[3462] Various technique for making and isolating bispecific antibodyfragments directly from recombinant cell culture have also beendescribed. For example, bispecific antibodies have been produced usingleucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992).The leucine zipper peptides from the Fos and Jun proteins were linked tothe Fab′ portions of two different antibodies by gene fusion. Theantibody homodimers were reduced at the hinge region to form monomersand then re-oxidized to form the antibody heterodimers. This method canalso be utilized for the production of antibody homodimers. The“diabody” technology described by Hollinger et al., Proc. Natl. Acad.Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism formaking bispecific antibody fragments. The fragments comprise aheavy-chain variable domain (V_(H)) connected to a light-chain variabledomain (V_(L)) by a linker which is too short to allow pairing betweenthe two domains on the same chain. Accordingly, the V_(H) and V_(L)domains of one fragment are forced to pair with the complementary V_(L)and V_(H) domains of another fragment, thereby forming twoantigen-binding sites. Another strategy for making bispecific antibodyfragments by the use of single-chain Fv (sFv) dimers has also beenreported. See, Gruber et al., J. Immunol. 152:5368 (1994). Antibodieswith more than two valencies are contemplated. For example, trispecificantibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[3463] Exemplary bispecific antibodies may bind to two differentepitopes on a given PRO polypeptide herein. Alternatively, an anti-PROpolypeptide arm may be combined with an arm which binds to a triggeringmolecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2,CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64),FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defensemechanisms to the cell expressing the particular PRO polypeptide.Bispecific antibodies may also be used to localize cytotoxic agents tocells which express a particular PRO polypeptide. These antibodiespossess a PRO-binding arm and an arm which binds a cytotoxic agent or aradionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Anotherbispecific antibody of interest binds the PRO polypeptide and furtherbinds tissue factor (TF).

[3464] 5. Heteroconugate Antibodies

[3465] Heteroconjugate antibodies are also within the scope of thepresent invention. Heteroconjugate antibodies are composed of twocovalently joined antibodies. Such antibodies have, for example, beenproposed to target immune system cells to unwanted cells [U.S. Pat. No.4,676,980], and for treatment of HIV infection [WO 91/00360; WO92/200373; EP 03089]. It is contemplated that the antibodies may beprepared in vitro using known methods in synthetic protein chemistry,including those involving crosslinking agents. For example, immunotoxinsmay be constructed using a disulfide exchange reaction or by forming athioether bond. Examples of suitable reagents for this purpose includeiminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, forexample, in U.S. Pat. No. 4,676,980.

[3466] 6. Effector Function Engineering

[3467] It may be desirable to modify the antibody of the invention withrespect to effector function, so as to enhance, e.g., the effectivenessof the antibody in treating cancer. For example, cysteine residue(s) maybe introduced into the Fc region, thereby allowing interchain disulfidebond formation in this region. The homodimeric antibody thus generatedmay have improved internalization capability and/or increasedcomplement-mediated cell killing and antibody-dependent cellularcytotoxicity (ADCC). See Caron et al., J. Ex Med., 176: 1191-1195(1992)and Shopes, J. Immunol., 148: 2918-2922(1992). Homodineric antibodieswith enhanced anti-tumor activity may also be prepared usingheterobifunctional cross-linkers as described in Wolff et al. CancerResearch, 53: 2560-2565 (1993). Alternatively, an antibody can beengineered that has dual Fc regions and may thereby have enhancedcomplement lysis and ADCC capabilities. See Stevenson et al.,Anti-Cancer Drug Design. 3: 219-230 (1989).

[3468] 7. Immunoconjugates

[3469] The invention also pertains to immunoconjugates comprising anantibody conjugated to a cytotoxic agent such as a chemotherapeuticagent, toxin (e.g., an enzymatically active toxin of bacterial, fungal,plant, or animal origin, or fragments thereof), or a radioactive isotope(i.e., a radioconjugate).

[3470] Chemotherapeutic agents useful in the generation of suchimmunoconjugates have been described above. Enzymatically active toxinsand fragments thereof that can be used include diphtheria A chain,nonbinding active fragments of diphtheria toxin, exotoxin A chain (fromPseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain,alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolacaanzericana proteins (PAPI, PAPII, and PAP-S), momordica charantiainhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin,mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. Avariety of radionuclides are available for the production ofradioconjugated antibodies. Examples include ²¹²Bi, ¹³¹I, ¹³¹In, ⁹⁰Y,and ¹⁸⁶Re. Conjugates of the antibody and cytotoxic agent are made usinga variety of bifunctional protein-coupling agents such asN-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane(IT), bifunctional derivatives of imidoesters (such as dimethyladipimidate HCL), active esters (such as disuccinimidyl suberate),aldehydes (such as glutareldehyde), bis-azido compounds (such as bis(p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such asbis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such astolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin canbe prepared as described in Vitetta et al., Science, 238: 1098 (1987).Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylenetriaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent forconjugation of radionucleotide to the antibody. See WO94/11026.

[3471] In another embodiment, the antibody may be conjugated to a“receptor” (such streptavidin) for utilization in tumor pretargetingwherein the antibody-receptor conjugate is administered to the patient,followed by removal of unbound conjugate from the circulation using aclearing agent and then administration of a “ligand” (e.g., avidin) thatis conjugated to a cytotoxic agent (e.g., a radionucleotide).

[3472] 8. Immunoliposomes

[3473] The antibodies disclosed herein may also be formulated asimmunoliposomes. Liposomes containing the antibody are prepared bymethods known in the art, such as described in Epstein et al., Proc.Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad.Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545.Liposomes with enhanced circulation time are disclosed in U.S. Pat. No.5,013,556.

[3474] Particularly useful liposomes can be generated by thereverse-phase evaporation method with a lipid composition comprisingphosphatidylcholine, cholesterol, and PEG-derivatizedphosphatidylethanolamine (PEG-PE). Liposomes are extruded throughfilters of defined pore size to yield liposomes with the desireddiameter. Fab′ fragments of the antibody of the present invention can beconjugated to the liposomes as described in Martin et al., J. Biol.Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. Achemotherapeutic agent (such as Doxorubicin) is optionally containedwithin the liposome. See Gabizon et al., J. National Cancer Inst.,81(19): 1484 (1989).

[3475] 9. Pharmaceutical Compositions of Antibodies

[3476] Antibodies specifically binding a PRO polypeptide identifiedherein, as well as other molecules identified by the screening assaysdisclosed hereinbefore, can be administered for the treatment of variousdisorders in the form of pharmaceutical compositions.

[3477] If the PRO polypeptide is intracellular and whole antibodies areused as inhibitors, internalizing antibodies are preferred. However,lipofections or liposomes can also be used to deliver the antibody, oran antibody fragment, into cells. Where antibody fragments are used, thesmallest inhibitory fragment that specifically binds to the bindingdomain of the target protein is preferred. For example, based upon thevariable-region sequences of an antibody, peptide molecules can bedesigned that retain the ability to bind the target protein sequence.Such peptides can be synthesized chemically and/or produced byrecombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad.Sci. USA, 90: 7889-7893 (1993). T h e formulation herein may alsocontain more than one active compound as necessary for the particularindication being treated, preferably those with complementary activitiesthat do not adversely affect each other. Alternatively, or in addition,the composition may comprise an agent that enhances its function, suchas, for example, a cytotoxic agent, cytoline, chemotherapeutic agent, orgrowth-inhibitory agent. Such molecules are suitably present incombination in amounts that are effective for the purpose intended.

[3478] The active ingredients may also be entrapped in microcapsulesprepared, for example, by coacervation techniques or by interfacialpolymerization, for example, hydroxymethylcellulose orgelatin-microcapsules and poly-(methylmethacylate) microcapsules,respectively, in colloidal drug delivery systems (for example,liposomes, albumin microspheres, microemulsions, nano-particles, andnanocapsules) or in macroemulsions. Such techniques are disclosed inRemington's Pharmaceutical Sciences, supra.

[3479] The formulations to be used for in vivo administration must besterile. This is readily accomplished by filtration through sterilefiltration membranes.

[3480] Sustained-release preparations may be prepared. Suitable examplesof sustained-release preparations include semipermeable matrices ofsolid hydrophobic polymers containing the antibody, which matrices arein the form of shaped articles, e.g., films, or microcapsules. Examplesof sustained-release matrices include polyesters, hydrogels (forexample, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)),polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acidand γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate,degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT(injectable microspheres composed of lactic acid-glycolic acid copolymerand leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. Whilepolymers such as ethylene-vinyl acetate and lactic acid-glycolic acidenable release of molecules for over 100 days, certain hydrogels releaseproteins for shorter time periods. When encapsulated antibodies remainin the body for a long time, they may denature or aggregate as a resultof exposure to moisture at 37° C., resulting in a loss of biologicalactivity and possible changes in immunogenicity. Rational strategies canbe devised for stabilization depending on the mechanism involved. Forexample, if the aggregation mechanism is discovered to be intermolecularS—S bond formation through thio-disulfide interchange, stabilization maybe achieved by modifying sulfhydryl residues, lyophilizing from acidicsolutions, controlling moisture content, using appropriate additives,and developing specific polymer matrix compositions.

[3481] G. Uses for Anti-PRO Antibodies

[3482] The anti-PRO antibodies of the invention have various utilities.For example, anti-PRO antibodies may be used in diagnostic assays forPRO, e.g., detecting its expression in specific cells, tissues, orserum. Various diagnostic assay techniques known in the art may be used,such as competitive binding assays, direct or indirect sandwich assaysand immunoprecipitation assays conducted in either heterogeneous orhomogeneous phases [Zola, Monoclonal Antibodies: A Manual of Techniques,CRC Press, Inc. (1987) pp. 147-158]. The antibodies used in thediagnostic assays can be labeled with a detectable moiety. Thedetectable moiety should be capable of producing, either directly orindirectly, a detectable signal. For example, the detectable moiety maybe a radioisotope, such as ³H, ¹⁴C, ³²P, ³⁵S, or ¹²⁵I, a fluorescent orchemiluminescent compound, such as fluorescein isothiocyanate,rhodanine, or luciferin, or an enzyme, such as alkaline phosphatase,beta-galactosidase or horseradish peroxidase. Any method known in theart for conjugating the antibody to the detectable moiety may beemployed, including those methods described by Hunter et al., Nature,144:945 (1962); David et al., Biochemistry, 13:1014 (1974); Pain et al.,J. Immunol. Meth., 40:219 (1981); and Nygren, J. Histochem. andCytochem., 30:407 (1982).

[3483] Anti-PRO antibodies also are useful for the affinity purificationof PRO from recombinant cell culture or natural sources. In thisprocess, the antibodies against PRO are immobilized on a suitablesupport, such a Sephadex resin or filter paper, using methods well knownin the art. The immobilized antibody then is contacted with a samplecontaining the PRO to be purified, and thereafter the support is washedwith a suitable solvent that will remove substantially all the materialin the sample except the PRO, which is bound to the immobilizedantibody. Finally, the support is washed with another suitable solventthat will release the PRO from the antibody.

[3484] The following examples are offered for illustrative purposesonly, and are not intended to limit the scope of the present inventionin any way.

[3485] All patent and literature references cited in the presentspecification are hereby incorporated by reference in their entirety.

EXAMPLES

[3486] Commercially available reagents referred to in the examples wereused according to manufacturer's instructions unless otherwiseindicated. The source of those cells identified in the followingexamples, and throughout the specification, by ATCC accession numbers isthe American Type Culture Collection, Manassas, Va.

Example 1 Extracellular Domain Homology Screening to Identify NovelPolypeptides and cDNA Encoding Therefor

[3487] The extracellular domain (ECD) sequences (including the secretionsignal sequence, if any) from about 950 known secreted proteins from theSwiss-Prot public database were used to search EST databases. The ESTdatabases included public databases (e.g., Dayhoff, GenBank), andproprietary databases (e.g. LIFESEQ™, Incyte Pharmaceuticals, Palo Alto,Calif.). The search was performed using the computer program BLAST orBLAST-2 (Altschul et al., Methods in Enzymology 266:460-480 (1996)) as acomparison of the ECD protein sequences to a 6 frame translation of theEST sequences. Those comparisons with a BLAST score of 70 (or in somecases 90) or greater that did not encode known proteins were clusteredand assembled into consensus DNA sequences with the program “phrap”(Phil Green, University of Washington, Seattle, Wash.).

[3488] Using this extracellular domain homology screen, consensus DNAsequences were assembled relative to the other identified EST sequencesusing phrap. In addition, the consensus DNA sequences obtained wereoften (but not always) extended using repeated cycles of BLAST orBLAST-2 and phrap to extend the consensus sequence as far as possibleusing the sources of EST sequences discussed above.

[3489] Based upon the consensus sequences obtained as described above,oligonucleotides were then synthesized and used to identify by PCR acDNA library that contained the sequence of interest and for use asprobes to isolate a clone of the full-length coding sequence for a PROpolypeptide. Forward and reverse PCR primers generally range from 20 to30 nucleotides and are often designed to give a PCR product of about100-1000 bp in length. The probe sequences are typically 40-55 bp inlength. In some cases, additional oligonucleotides are synthesized whenthe consensus sequence is greater than about 1-1.5 kbp. In order toscreen several libraries for a full-length clone, DNA from the librarieswas screened by PCR amplification, as per Ausubel et al., CurrentProtocols in Molecular Biology, with the PCR primer pair. A positivelibrary was then used to isolate clones encoding the gene of interestusing the probe oligonucleotide and one of the primer pairs.

[3490] The cDNA libraries used to isolate the cDNA clones wereconstructed by standard methods using commercially available reagentssuch as those from Invitrogen, San Diego, Calif. The cDNA was primedwith oligo dT containing a NotI site, linked with blunt to SalIhernikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

Example 2 Isolation of cDNA Clones by Amylase Screening

[3491] 1. Preparation of Oligo dT Primed cDNA Library

[3492] mRNA was isolated from a human tissue of interest using reagentsand protocols from Invitrogen, San Diego, Calif. (Fast Track 2). ThisRNA was used to generate an oligo dT primed cDNA library in the vectorpRK5D using reagents and protocols from Life Technologies, Gaithersburg,Md. (Super Script Plasmid System). In this procedure, the doublestranded cDNA was sized to greater than 1000 bp and the SalI/NotITinkered cDNA was cloned into XhoI/NotI cleaved vector. pRK5D is acloning vector that has an sp6 transcription initiation site followed byan SfiI restriction enzyme site preceding the XhoI/NotI cDNA cloningsites.

[3493] 2. Preparation of Random Primed cDNA Library

[3494] A secondary cDNA library was generated in order to preferentiallyrepresent the 5′ ends of the primary cDNA clones. Sp6 RNA was generatedfrom the primary library (described above), and this RNA was used togenerate a random primed cDNA library in the vector pSST-AMY.0 usingreagents and protocols from Life Technologies (Super Script PlasmidSystem, referenced above). In this procedure the double stranded cDNAwas sized to 500-1000 bp, Tinkered with blunt to NotI adaptors, cleavedwith SfiI, and cloned into SfiI/NotI cleaved vector. pSST-AMY.0 is acloning vector that has a yeast alcohol dehydrogenase promoter precedingthe cDNA cloning sites and the mouse amylase sequence (the maturesequence without the secretion signal) followed by the yeast alcoholdehydrogenase terminator, after the cloning sites. Thus, cDNAs clonedinto this vector that are fused in frame with amylase sequence will leadto the secretion of amylase from appropriately transfected yeastcolonies.

[3495] 3. Transformation and Detection

[3496] DNA from the library described in paragraph 2 above was chilledon ice to which was added electrocompetent DH10B bacteria (LifeTechnologies, 20 ml). The bacteria and vector mixture was thenelectroporated as recommended by the manufacturer. Subsequently, SOCmedia (Life Technologies, 1 ml) was added and the mixture was incubatedat 37° C. for 30 minutes. The transformants were then plated onto 20standard 150 mm LB plates containing ampicillin and incubated for 16hours (37° C.). Positive colonies were scraped off the plates and theDNA was isolated from the bacterial pellet using standard protocols,e.g. CsCl-gradient. The purified DNA was then carried on to the yeastprotocols below.

[3497] The yeast methods were divided into three categories: (1)Transformation of yeast with the plasmid/cDNA combined vector; (2)Detection and isolation of yeast clones secreting amylase; and (3) PCRamplification of the insert directly from the yeast colony andpurification of the DNA for sequencing and further analysis.

[3498] The yeast strain used was HD56-5A (ATCC-90785). This strain hasthe following genotype: MAT alpha, ura3-52, leu2-3, leu2-112, his3-11,his3-15, MAL⁺, SUC⁺, GAL⁺. Preferably, yeast mutants can be employedthat have deficient post-translational pathways. Such mutants may havetranslocation deficient alleles in sec71, sec72, sec62, with truncatedsec71 being most preferred. Alternatively, antagonists (includingantisense nucleotides and/or ligands) which interfere with the normaloperation of these genes, other proteins implicated in this posttranslation pathway (e.g., SEC61p, SEC72p, SEC62p, SEC63p, TDJ1p orSSA1p-4p) or the complex formation of these proteins may also bepreferably employed in combination with the amylase-expressing yeast.

[3499] Transformation was performed based on the protocol outlined byGietz et al., Nucl. Acid. Res., 20:1425 (1992). Transformed cells werethen inoculated from agar into YEPD complex media broth (100 ml) andgrown overnight at 30° C. The YEPD broth was prepared as described inKaiser et al., Methods in Yeast Genetics, Cold Spring Harbor Press, ColdSpring Harbor, N.Y., p. 207 (1994). The overnight culture was thendiluted to about 2×10⁶ cells/ml (approx. OD₆₀₀=0.1) into fresh YEPDbroth (500 ml) and regrown to 1×10⁷ cells/ml (approx. OD₆₀₀=0.4-0.5).

[3500] The cells were then harvested and prepared for transformation bytransfer into GS3 rotor bottles in a Sorval GS3 rotor at 5,000 rpm for 5minutes, the supernatant discarded, and then resuspended into sterilewater, and centrifuged again in 50 ml falcon tubes at 3,500 rpm in aBeckman GS-6KR centrifuge. The supernatant was discarded and the cellswere subsequently washed with LiAc/TE (10 ml, 10 mM Tris-HCl, 1 mM EDTApH 7.5, 100 mM Li₂OOCCH₃), and resuspended into LiAc/TE (2.5 ml).

[3501] Transformation took place by mixing the prepared cells (100 μl)with freshly denatured single stranded salmon testes DNA (LofstrandLabs, Gaithersburg, Md.) and transforming DNA (1 μg, vol. <10 μl) inmicrofuge tubes. The mixture was mixed briefly by vortexing, then 40%PEG/TE (600 μl, 40% polyethylene glycol-4000, 10 mM Tris-HCl, 1 mM EDTA,100 mM Li₂OOCCH₃, pH 7.5) was added. This mixture was gently mixed andincubated at 30° C. while agitating for 30 minutes. The cells were thenheat shocked at 42° C. for 15 minutes, and the reaction vesselcentrifuged in a microfuge at 12,000 rpm for 5-10 seconds, decanted andresuspended into TE (500 μl, 10 mM Tris-HCl, 1 mM EDTA pH 7.5) followedby recentrifugation. The cells were then diluted into TE (1 ml) andaliquots (200 μl) were spread onto the selective media previouslyprepared in 150 mm growth plates (VWR).

[3502] Alternatively, instead of multiple small reactions, thetransformation was performed using a single, large scale reaction,wherein reagent amounts were scaled up accordingly.

[3503] The selective media used was a synthetic complete dextrose agarlacking uracil (SCD-Ura) prepared as described in Kaiser et al., Methodsin Yeast Genetics, Cold Spring Harbor Press, Cold Spring Harbor, N.Y.,p. 208-210 (1994). Transformants were grown at 30° C. for 2-3 days.

[3504] The detection of colonies secreting amylase was performed byincluding red starch in the selective growth media. Starch was coupledto the red dye (Reactive Red-120, Sigma) as per the procedure describedby Biely et al., Anal. Biochem., 172:176-179 (1988). The coupled starchwas incorporated into the SCD-Ura agar plates at a final concentrationof 0.15% (w/v), and was buffered with potassium phosphate to a pH of 7.0(50-100 mM final concentration).

[3505] The positive colonies were picked and streaked across freshselective media (onto 150 mm plates) in order to obtain well isolatedand identifiable single colonies. Well isolated single colonies positivefor amylase secretion were detected by direct incorporation of redstarch into buffered SCD-Ura agar. Positive colonies were determined bytheir ability to break down starch resulting in a clear halo around thepositive colony visualized directly.

[3506] 4. Isolation of DNA by PCR Amplification

[3507] When a positive colony was isolated, a portion of it was pickedby a toothpick and diluted into sterile water (30 μl) in a 96 wellplate. At this time, the positive colonies were either frozen and storedfor subsequent analysis or immediately amplified. An aliquot of cells (5μl) was used as a template for the PCR reaction in a 25 μl volumecontaining: 0.5 μl Klentaq (Clontech, Palo Alto, Calif.); 4.0 μl 10 mMdNTP's (Perkin Elmer-Cetus); 2.5 μl Kentaq buffer (Clontech); 0.25 μlforward oligo 1; 0.25 μl reverse oligo 2; 12.5 μl distilled water. Thesequence of the forward oligonucleotide 1 was:5′-TGTAAAACGACGGCCAGTTAAATAGACCTGCAATTATTAATCT-3′ (SEQ ID NO:3)

[3508] The sequence of reverse oligonucleotide 2 was:5′-CAGGAAACAGCTATGACCACCTGCACACCTGCAAATCCATT-3′ (SEQ ID NO:4)

[3509] PCR was then performed as follows: a. Denature 92° C.,  5 minutesb.  3 cycles of: Denature 92° C., 30 seconds Anneal 59° C., 30 secondsExtend 72° C., 60 seconds c.  3 cycles of: Denature 92° C., 30 secondsAnneal 57° C., 30 seconds Extend 72° C., 60 seconds d. 25 cycles of:Denature 92° C., 30 seconds Anneal 55° C., 30 seconds Extend 72° C., 60seconds e. Hold  4° C.,

[3510] The underlined regions of the oligonucleotides annealed to theADH promoter region and the amylase region, respectively, and amplifieda 307 bp region from vector pSST-AMY.0 when no insert was present.Typically, the first 18 nucleotides of the 5′ end of theseoligonucleotides contained annealing sites for the sequencing primers.Thus, the total product of the PCR reaction from an empty vector was 343bp. However, signal sequence-fused cDNA resulted in considerably longernucleotide sequences.

[3511] Following the PCR, an aliquot of the reaction (5 μl) was examinedby agarose gel electrophoresis in a 1% agarose gel using aTris-Borate-EDTA (TBE) buffering system as described by Sambrook et al.,supra. Clones resulting in a single strong PCR product larger than 400bp were further analyzed by DNA sequencing after purification with a 96Qiaquick PCR clean-up column (Qiagen Inc., Chatsworth, Calif.).

Example 3 Isolation of cDNA Clones Using Signal Algorithm Analysis

[3512] Various polypeptide-encoding nucleic acid sequences wereidentified by applying a proprietary signal sequence finding algorithmdeveloped by Genentech, Inc. (South San Francisco, Calif.) upon ESTs aswell as clustered and assembled EST fragments from public (e.g.,GenBank) and/or private (LIFESEQ®, Incyte Pharmaceuticals, Inc., PaloAlto, Calif.) databases. The signal sequence algorithm computes asecretion signal score based on the character of the DNA nucleotidessurrounding the first and optionally the second methionine codon(s)(ATG) at the 5′-end of the sequence or sequence fragment underconsideration. The nucleotides following the first ATG must code for atleast 35 unambiguous amino acids without any stop codons. If the firstATG has the required amino acids, the second is not examined. If neithermeets the requirement, the candidate sequence is not scored. In order todetermine whether the EST sequence contains an authentic signalsequence, the DNA and corresponding amino acid sequences surrounding theATG codon are scored using a set of seven sensors (evaluationparameters) known to be associated with secretion signals. Use of thisalgorithm resulted in the identification of numerouspolypeptide-encoding nucleic acid sequences.

Example 4 Isolation of cDNA Clones Encoding Human PRO281

[3513] In order to obtain a cDNA clone encoding PRO281, methodsdescribed in Klein et al., Proc. Natl. Acad. Sci. USA 93:7108-7113(1996) were employed with the following modifications. Yeasttransformation was performed with limiting amounts of transforming DNAin order to reduce the number of multiple transformed yeast cells.Instead of plasmid isolation from the yeast followed by transformationof E. coli as described in Klein et al., supra, PCR analysis wasperformed on single yeast colonies. PCR primers employed were bipartitein order to amplify the insert and a small portion of the invertase gene(allowing to determine that the insert was in frame with invertase) andto add on universal sequencing primer sites.

[3514] An invertase library was transformed into yeast and positiveswere selected on sucrose plates. Positive clones were re-tested and PCRproducts were sequenced. The sequence of one clone, PRO281, wasdetermined to contain a signal peptide coding sequence. Oligonucleotideprimers and probes were designed using the nucleotide sequence ofPRO281. A full length plasmid library of cDNAs from human umbilical veinendothelium tissue was titered and approximately 100,000 cfu were platedin 192 pools of 500 cfu/pool into 96-well round bottom plates. Theplates were sealed and pools were grown overnight at 37° C. with shaking(200 rpm). PCR was performed on the individual cultures using primers.Agarose gel electrophoresis was performed and positive wells wereidentified by visualization of a band of the expected size. Individualpositive clones were obtained by colony lift followed by hybridizationwith ³²P-labeled oligonucleotide. These clones were characterized byPCR, restriction digest, and southern blot analyses.

[3515] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 80-82, and a stop signal at nucleotide positions1115-1117 (FIG. 1, SEQ ID NO:1). The predicted polypeptide precursor is345 amino acids long, has a calculated molecular weight of approximately37,205 daltons and an estimated pI of approximately 10.15. Analysis ofthe full-length PRO281 sequence shown in FIG. 2 (SEQ ID NO:2) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 14, multiple transmembrane domains from about aminoacid position 83 to about amino acid position 105, from about amino acidposition 126 to about amino acid position 146, from about amino acidposition 158 to about amino acid position 177, from about amino acidposition 197 to about amino acid position 216, from about amino acidposition 218 to about amino acid position 238, from about amino acidposition 245 to about amino acid position 265, and from about amino acidposition 271 to about amino acid position 290 and an amino acid sequenceblock having homology to G-protein coupled receptor proteins from aboutamino acid 115 to about amino acid 155. Clone UNQ244 (DNA16422-1209) hasbeen deposited with ATCC on Jun. 2, 1998 and is assigned ATCC depositno. 209929.

[3516] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 2 (SEQ ID NO:2), evidenced significant homologybetween the PRO281 amino acid sequence and the following Dayhoffsequences: H64634, AF033095_(—)1, B64815, YBHL_ECOLI, EMEQUTR_(—)1,AF064763_(—)3, S53708, A69253, AF035413_(—)12 and S63281.

Example 5 Isolation of cDNA Clones Encoding Human PRO276

[3517] In order to obtain a cDNA clone encoding PRO276, methodsdescribed in Klein et al., PNAS, 93:7108-7113 (1996) were employed withthe following modifications. Yeast transformation was performed withlimiting amounts of transforming DNA in order to reduce the number ofmultiple transformed yeast cells. Instead of plasmid isolation from theyeast followed by transformation of E. coli as described in Klein etal., supra, PCR analysis was performed on single yeast colonies. PCRprimers employed were bipartite in order to amplify the insert and asmall portion of the invertase gene (allowing to determine that theinsert was in frame with invertase) and to add on universal sequencingprimer sites.

[3518] An invertase library was transformed into yeast and positiveswere selected on sucrose plates. Positive clones were re-tested and PCRproducts were sequenced. The sequence of one clone, PRO276, wasdetermined to contain a signal peptide coding sequence. Oligonucleotideprimers and probes were designed using the nucleotide sequence ofPRO276. A full length plasmid library of cDNAs from human fetal livercells was titered and approximately 100,000 cfu were plated in 192 poolsof 500 cfu/pool into 96-well round bottom plates. The plates were sealedand pools were grown overnight at 37 C with shaking (200 rpm). PCR wasperformed on the individual cultures using primers. Agarose gelelectrophoresis was performed and positive wells were identified byvisualization of a band of the expected size. Individual positive cloneswere obtained by colony lift followed by hybridization with ³²P-labeledoligonucleotide. These clones were characterized by PCR, restrictiondigest, and southern blot analyses.

[3519] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 180-182 and a stop signal at nucleotide positions933-935 (FIG. 3; SEQ ID NO:5). The predicted polypeptide precursor is251 amino acids long has a calculated molecular weight of approximately28,801 daltons and an estimated pI of approximately 9.58. Thetransmembrane domains are approximately at amino acids 98-116 and152-172 of the sequence shown in FIG. 4 (SEQ ID NO:6). CloneDNA16435-1208 (UNQ243) has been deposited with the ATCC and is assignedATCC deposit no. 209930.

[3520] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 4 (SEQ ID NO:6), revealed some sequence identitybetween the PRO276 amino acid sequence and the following Dayhoffsequences: CEG25D7_(—)2, ATT8O5_(—)2, S69696, GRHR_RAT, NPCBAABCD_(—)3,AB013149_(—)1, P_R85942 and AP000006_(—)5.

Example 6 Isolation of cDNA Clones Encoding Human PRO189

[3521] A clone designated herein as DNA14187 was isolated as describedin Example 2 above from a human retina tissue library. The DNA14187sequence is shown in FIG. 7 (SEQ ID NO:9). Based on the DNA14187sequence shown in FIG. 7 (SEQ ID NO:9), oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO189. Forward and reverse PCR primersgenerally range from 20 to 30 nucleotides and are often designed to givea PCR product of about 100-1000 bp in length. The probe sequences aretypically 40-55 bp in length. In order to screen several libraries for afull-length clone, DNA from the libraries was screened by PCRamplification, as per Ausubel et al., Current Protocols in MolecularBiology, with the PCR primer pair. A positive library was then used toisolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

[3522] A pair of PCR primers (forward and reverse) were synthesized:forward PCR primer 5′-TTGACCTATACAGAGATTCATC-3′ (SEQ ID NO:10); andreverse PCR primer 5′-CTAAGAACTTCCCTCAGGATTTT-3′ (SEQ ID NO:11).

[3523] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA14187 sequence which had the followingnucleotide sequence: hybridization probe5′-ATGAAGATCAATTTCAAGAAGCATGCACTTCTCCTCTTGC-3′ (SEQ ID NO:12).

[3524] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO189 gene usingthe probe oligonucleotide and one of the PCR primers.

[3525] RNA for construction of the cDNA libraries was isolated fromhuman retina tissue (LIB94). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3526] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO189 and the derived protein sequence forPRO189.

[3527] The entire nucleotide sequence of DNA21624-1391 is shown in FIG.5 (SEQ ID NO:7). Clone DNA21624-1391 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 200-202 and ending at the stop codon at nucleotide positions1301-1303 (FIG. 5). The predicted polypeptide precursor is 367 aminoacids long (FIG. 6). The full-length PRO189 protein shown in FIG. 6 hasan estimated molecular weight of about 41,871 daltons and a pI of about5.06. Clone DNA21624-1391 has been deposited with the ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

[3528] Analyzing the amino acid sequence of SEQ ID NO:8, the putativeN-glycosylation sites are at about amino acids 224-227, 246-249 and285-288. A domain for cytosolic fatty-acid binding proteins is at aminoacids 78-107 of SEQ ID NO:8. The corresponding nucleotides can beroutinely determined given the sequences provided herein.

[3529] Some sequence identity was found to W01A6.1 and F35D11.11, C.Elegans proteins, designated in a Dayhoff database as CEW01A6_(—)10 andCELF35D11_(—)11, respectively. Some sequence identity was also found toan antigen to malaria and to restin, designated in a Dayhoff database asP_R05766 and AF014012_(—)1, respectively. Some sequence identity wasalso found to a microtubule binding protein and to myosin, designated ina Dayhoff database as AF041382_(—)1 and S07537, respectively. There isalso some sequence identity with1-phosphatidylinositol-4,5-bisphosphate, designated as PIP1_RAT.

Example 7 Isolation of cDNA Clones Encoding Human PRO190

[3530] A clone designated herein as DNA14232 was isolated as describedin Example 2 above from a human fetal retina tissue library. TheDNA14232 sequence is shown in FIG. 10 (SEQ ID NO:15). Based on theDNA14232 sequence, oligonucleotides were synthesized: 1) to identify byPCR a cDNA library that contained the sequence of interest, and 2) foruse as probes to isolate a clone of the full-length coding sequence forPRO190. Forward and reverse PCR primers generally range from 20 to 30nucleotides and are often designed to give a PCR product of about100-1000 bp in length. The probe sequences are typically 40-55 bp inlength. In order to screen several libraries for a full-length clone,DNA from the libraries was screened by PCR amplification, as per Ausubelet al., Current Protocols in Molecular Biology, with the PCR primerpair. A positive library was then used to isolate clones encoding thegene of interest using the probe oligonucleotide and one of the primerpairs.

[3531] A pair of PCR primers (forward and reverse) were synthesized:forward PCR primer 5′-CTATACCTACTGTAGCTTCT-3′ (SEQ ID NO:16); andreverse PCR primer 5′-TCAGAGAATTCCTTCCAGGA-3′ (SEQ ID NO:17).

[3532] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA14232 sequence which had the followingnucleotide sequence: hybridization probe5′-ACAGTGCTGTAGTCATCCTGTAATATGCTCCTTGTCAACA-3′ (SEQ ID NO:18).

[3533] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO190 gene usingthe probe oligonucleotide and one of the PCR primers.

[3534] RNA for construction of the cDNA libraries was isolated fromhuman retina tissue (LIB94). The cDNA libraries used to isolate the cDNAclones were constructed by standard methods using commercially availablereagents such as those from Invitrogen, San Diego, Calif. The cDNA wasprimed with oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRKSB is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3535] DNA sequencing of the clones isolated as described above gavesequences which include the full-length DNA sequence for PRO190 [hereindesignated as DNA23334-1392] (SEQ ID NO:13) and the derived proteinsequence for PRO190.

[3536] The entire nucleotide sequence of DNA23334-1392 is shown in FIG.8 (SEQ ID NO:13). Clone DNA23334-1392 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 193-195 and which ends at the stop codon at nucleotidepositions 1465-1467 (FIG. 8). The predicted polypeptide precursor is 424amino acids long (FIG. 9). The full-length PRO190 protein shown in FIG.9 has an estimated molecular weight of about 48,500 daltons and a pI ofabout 8.65. Clone DNA23334-1392 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

[3537] Analyzing the amino acid sequence of SEQ ID NO:14, the putativetransmembrane domains are at about amino acids 16-36, 50-74, 147-168,229-250, 271-293, 298-318 and 328-368 of SEQ ID NO:14. N-glycosylationsites are at about amino acids 128-131, 204-207, 218-221 and 274-377 ofSEQ ID NO:14. The corresponding nucleotides can be routinely determinedgiven the sequences provided herein.

[3538] PRO190 has sequence identity with at least the following Dayhoffsequences designated as: CEZK896_(—)2, JC5023, GMS1_SCHPO and S44668.

Example 8 Isolation of cDNA Clones Encoding Human PRO341

[3539] A clone designated herein as DNA12920 was isolated as describedin Example 2 above from a human placenta tissue library. The DNA12920sequence is shown in FIG. 13 (SEQ ID NO:21). The DNA12920 sequence wasthen compared to various EST databases including public EST databases(e.g., GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460-480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence is herein designated DNA25314. Oligonucleotide primers basedupon the DNA25314 sequence were then synthesized and employed to screena human placenta cDNA library which resulted in the identification ofthe DNA26288-1239 clone shown in FIG. 11. The cloning vector was pRK5B(pRK5B is a precursor of pRK5D that does not contain the SfiI site; see,Holmes et al., Science, 253:1278-1280 (1991)), and the cDNA size cut wasless than 2800 bp.

[3540] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 380-382, and a stop signal at nucleotide positions1754-1756 (FIG. 11, SEQ ID NO:19). The predicted polypeptide precursoris 458 amino acids long, has a calculated molecular weight ofapproximately 50,264 daltons and an estimated pI of approximately 8.17.Analysis of the full-length PRO341 sequence shown in FIG. 12 (SEQ IDNO:20) evidences the presence of the following: a signal peptide fromabout amino acid 1 to about amino acid 17, transmembrane domains fromabout amino acid 171 to about amino acid 190, from about amino acid 220to about amino acid 239, from about amino acid 259 to about amino acid275, from about amino acid 286 to about amino acid 305, from about aminoacid 316 to about amino acid 335, from about amino acid 353 to aboutamino acid 378 and from about amino acid 396 to about amino acid 417 andpotential N-glycosylation sites from about amino acid 145 to about aminoacid 147 and from about amino acid 155 to about amino acid 158. CloneDNA26288-1239 has been deposited with ATCC on Apr. 21, 1998 and isassigned ATCC deposit no. 209792.

[3541] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 12 (SEQ ID NO:20), evidenced homology between thePRO341 amino acid sequence and the following Dayhoff sequences: S75696,H69788, D69852, A69888, B64918, F64752, LPU89276_(—)1, G64962, S52977and S44253.

Example 9 Isolation of cDNA Clones Encoding Human PRO180

[3542] A clone designated herein as DNA12922 was isolated as describedin Example 2 above from a human placenta tissue library. The DNA12922sequence is shown in FIG. 16 (SEQ ID NO:24). The DNA12922 sequence wasthen compared to various EST databases including public EST databases(e.g., GenBank), and a proprietary EST database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460-480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.).

[3543] An oligonucleotide probe was formed based upon the consensussequence obtained above. This probe had the following sequence.5′-ACCTGTTAGAAATGTGGTGGTTTCAGCAAGGCCTCAGTTT (SEQ ID NO:25).

[3544] This probe was used to screen a human placenta library preparedas described in paragraph 1 of Example 2 above. The cloning vector waspRK5B (pRK5B is a precursor of pRK5D that does not contain the SfiIsite; see, Holmes et al., Science, 253: 1278-1280 (1991)), and the cDNAsize cut was less than 2800 bp. A clone designated herein asDNA26843-1389 was obtained.

[3545] The entire nucleotide sequence of DNA26843-1389 is shown in FIG.14 (SEQ ID NO:22). Clone DNA26843-1389 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 121-123 and ending at the stop codon at nucleotide positions919-921 (FIG. 14). The predicted polypeptide precursor is 266 aminoacids long (FIG. 15). The full-length PRO180 protein shown in FIG. 15has an estimated molecular weight of about 29,766 daltons and a pI ofabout 8.39. Clone DNA26843-1389 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

[3546] Still analyzing the amino acid sequence of SEQ ID NO:23, thetransmembrane domains are at about amino acids 13-33 (type II), 54-73,94-113, 160-180 and 122-141 of SEQ ID NO:23. N-myristoylation sites areat about amino acids 57-62, 95-100, 99-104, 124-129 and 183-188 of SEQID NO:23. The corresponding nucleotides can be routinely determinedgiven the sequences provided herein.

[3547] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST2 sequence alignment analysis of the full-lengthsequence shown in FIG. 15 (SEQ ID NO:23), evidenced some sequenceidentity between the PRO180 amino acid sequence and the followingDayhoff sequences: CEC33A11_(—)2, CEG11E6_(—)5, CELW03A5_(—)1 ANDPEU83861_(—)2 (NADH dehydrogenase subunit 4L, mitochondrion).

Example 10 Isolation of cDNA Clones Encoding Human PRO194

[3548] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This consensussequence is herein DNA19464. Based on the DNA19464 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO194. PCRprimers (forward and reverse) were synthesized based upon the DNA19464sequence. Additionally, a synthetic oligonucleotide hybridization probewas constructed from the consensus DNA19464 sequence.

[3549] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO194 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal lungtissue (LIB25).

[3550] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO194 [herein designated as DNA26844-1394](SEQ ID NO:27) and the derived protein sequence for PRO194.

[3551] The entire nucleotide sequence of DNA26844-1394 is shown in FIG.17 (SEQ ID NO:27). Clone DNA26844-1394 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 81-83 and ending at the stop codon at nucleotide positions873-875 (FIG. 17). The predicted polypeptide precursor is 264 aminoacids long (FIG. 18). The full-length PRO194 protein shown in FIG. 18has an estimated molecular weight of about 29,665 daltons and a pI ofabout 9.34. Analysis of the full-length PRO194 sequence shown in FIG. 18(SEQ ID NO:28) evidences the presence of various important polypeptidesdomains as shown in FIG. 18. Clone DNA26844-1394 has been deposited withATCC on Jun. 2, 1998 and is assigned ATCC deposit no. 209926.

[3552] Analysis of the amino acid sequence of the full-length PRO194polypeptide suggests that it does not exhibit significant sequencesimilarity to any known human protein. However, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced some homologybetween the PRO194 amino acid sequence and the following Dayhoffsequences, HUMORFT_(—)1, CET07F10_(—)5, ATFCA9_(—)12, F64934,YDJX_ECOLI, ATAF00065719F29G20.19, H70002, S76980, H64934 and S76385.

Example 11 Isolation of cDNA Clones Encoding Human PRO203

[3553] A clone designated herein as DNA15618 was isolated as describedin Example 2 above from a human fetal lung tissue library. The DNA15618sequence is shown in FIG. 21 (SEQ ID NO:31). Oligonucleotide probes weregenerated from the sequence of the DNA15618 molecule and were used toscreen a human fetal lung library (LIB26) prepared as described inparagraph 1 of Example 2 above. The cloning vector was pRK5B (pRK5B is aprecursor of pRK5D that does not contain the SfiI site; see, Holmes etal., Science, 253:1278-1280 (1991)), and the cDNA size cut was less than2800 bp.

[3554] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 159-161 and ending at the stop codon found atnucleotide positions 1200-1202 (FIG. 19; SEQ ID NO:29). The predictedpolypeptide precursor is 347 amino acids long, has a calculatedmolecular weight of approximately 39,870 daltons and an estimated pI ofapproximately 6.76. Analysis of the full-length PRO203 sequence shown inFIG. 20 (SEQ ID NO:30) evidences the presence of the following: a typeII transmembrane domain at about amino acid 64 to about amino acid 87;possible N-glycosylation sites at about amino acid 147 to about aminoacid 150, about amino acid 155 to about amino acid 158, and about aminoacid 237 to about amino acid 240; sequence identity withheavy-metal-associated domain proteins at about amino acid 23 to aboutamino acid 45, and sequence identity with D-isomer specific2-hydroxyacid dehydrogenase at about amino acid 24 to about amino acid34. Clone DNA30862-1396 was deposited with the ATCC on Jun. 2, 1998, andis assigned ATCC deposit no. 209920.

[3555] Analysis of the amino acid sequence of the full-length PRO203polypeptide suggests that it possesses sequence similarity to GSTATPase, thereby indicating that PRO203 may be a novel GST ATPase. Morespecifically, an analysis of the Dayhoff database (version 35.45SwissProt 35) evidenced homology between the PRO203 amino acid sequenceand the following Dayhoff sequences, AF008124_(—)1, CFRCD1GEN_(—)1, andP_R82566.

Example 12 Isolation of cDNA Clones Encoding Human PRO290

[3556] An expressed sequence tag (EST) DNA database (LIFESEQ®, IncytePharmaceuticals, Palo Alto, Calif.) was searched and an EST wasidentified that had homology to beige and FAN. An oligonucleotide probebased upon the identified EST sequence was then synthesized and used toscreen human fetal kidney cDNA libraries in an attempt to identify afull-length cDNA clone. The oligonucleotide probe had the followingsequence: 5′ TGACTGCACTACCCCGTGGCAAGCTGTTGAGCCAGCTCAGCTG 3′ (SEQ IDNO:34).

[3557] RNA for construction of cDNA libraries was isolated from humanfetal kidney tissue. The cDNA libraries used to isolate the cDNA clonesencoding human PRO290 were constructed by standard methods usingcommercially available reagents such as those from Invitrogen, SanDiego, Calif. The cDNA was primed with oligo dT containing a NotI site,linked with blunt to SalI hemikinased adaptors, cleaved with NotI, sizedappropriately by gel electrophoresis, and cloned in a definedorientation into a suitable cloning vector (such as pRKB or pRKD; pRK5Bis a precursor of pRK5D that does not contain the SfiI site; see, Holmeset al., Science 253:1278-1280 (1991)) in the unique XhoI and NotI.

[3558] A cDNA clone was identified and sequenced in entirety. The entirenucleotide sequence of DNA35680-1212 is shown in FIG. 22 (SEQ ID NO:32).Clone DNA35680-1212 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 293-295,and a stop codon at nucleotide positions 3302-3304 (FIG. 22; SEQ IDNO:32). The predicted polypeptide precursor is 1003 amino acids long.

[3559] It is currently believed that the PRO290 polypeptide is relatedto FAN and/or beige. Clone DNA35680-1212 has been deposited with ATCCand is assigned ATCC deposit no. 209790. It is understood that thedeposited clone has the actual correct sequence rather than therepresentations provided herein. The full-length PRO290 protein shown inFIG. 23 has an estimated molecular weight of about 112,013 daltons -anda pI of about 6.4.

Example 13 Isolation of cDNA Clones Encoding Human PRO874

[3560] A consensus DNA sequence designated herein as DNA36459 wasidentified using phrap as described in Example 1 above. Based on theDNA36459 consensus sequence, oligonucleotides were synthesized: 1) toidentify by PCR a cDNA library that contained the sequence of interest,and 2) for use as probes to isolate a clone of the coding sequence forPRO874.

[3561] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-TCGTGCCCAGGGGCTGATGTGC-3′ (SEQ ID NO:37); and reverse PCRprimer 5′-GTCTTTACCCAGCCCCGGGATGCG-3′ (SEQ ID NO:38).

[3562] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA36459 sequence which had the followingnucleotide sequence: hybridization probe5′-GGCCTAATCCAACGTTCTGTCTTCAATCTGCAAATCTATGGGGTCCTGGG-3′ (SEQ ID NO:39).

[3563] In order to screen several libraries for a source of a clone, DNAfrom the libraries was screened by PCR amplification with the PCR primerpair identified above. A positive library was then used to isolateclones encoding the PRO874 gene using the probe oligonucleotide and oneof the PCR primers. RNA for construction of the cDNA libraries wasisolated from human fetal lung tissue (LIB25).

[3564] DNA sequencing of the clones isolated as described above gave theDNA sequence for PRO874 [herein designated as DNA40621-1440] (SEQ IDNO:35) and the derived protein sequence for PRO874.

[3565] The entire nucleotide sequence of DNA40621-1440 is shown in FIG.24 (SEQ ID NO:35). Clone DNA40621-1440 contains a single open readingframe ending at the stop codon at nucleotide positions 964-966 (FIG.24). The predicted polypeptide encoded by DNA40621-1440 is 321 aminoacids long (FIG. 25). The PRO874 protein shown in FIG. 25 has anestimated molecular weight of about 36,194 daltons and a pI of about9.85. Analysis of the PRO874 sequence shown in FIG. 25 (SEQ ID NO:36)evidenced the presence of the following: a type II transmembrane domainat about amino acids 57-80; additional transmembrane domains at aboutamino acids 110-126, 215-231, and 254-274; potential N-glycosylationsites at about amino acids 16-19, 27-30, and 289-292; sequence identitywith hypothetical YBR102c family proteins at about amino acids 276-287;and sequence identity with ammonium transporter proteins at about aminoacids 204-230. Clone DNA40621-1440 was deposited with the ATCC on Jun.2, 1998, and is assigned ATCC deposit no. 209922.

[3566] Analysis of the amino acid sequence of the PRO874 polypeptidesuggests that it is a novel multi-span transmembrane protein. However,an analysis of the Dayhoff database (version 35.45 SwissProt 35)evidenced sequence identity between the PRO874 amino acid sequence andthe following Dayhoff sequences: S67049, AF054839_(—)1, S73437, S52460,and HIVU80570_(—)1.

Example 14 Isolation of cDNA Clones Encoding Human PRO710

[3567] A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA38190) is shown in FIG. 28 (SEQ ID NO:42). Based on theDNA38190 sequence shown in FIG. 28, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO710. In order to screen severallibraries for a full-length clone, DNA from the libraries was screenedby PCR amplification, as per Ausubel et al., Current Protocols inMolecular Biology, with the PCR primer pair. A positive library was thenused to isolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

[3568] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-TTCCGCAAAGAGTTCTACGAGGTGG-3′ (SEQ ID NO:43) reverse PCR primer5′-ATTGACAACATTGACTGGCCTATGGG-3′ (SEQ ID NO:44)

[3569] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA38190 sequence which had the followingnucleotide sequence hybridization probe5′-GTGGATGCTCTGTGTGCGTGCAAGATCCTTCAGGCCTTGTTCCAGTGTGA-3′ (SEQ ID NO:45)

[3570] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO710 gene usingthe probe oligonucleotide and one of the PCR primers.

[3571] RNA for construction of the cDNA libraries was isolated fromhuman fetal kidney tissue (LIB227). The cDNA libraries used to isolatethe cDNA clones were constructed by standard methods using commerciallyavailable reagents such as those from Invitrogen, San Diego, Calif. ThecDNA was primed with oligo dT containing a NotI site, linked with bluntto SalI hemikinased adaptors, cleaved with NotI, sized appropriately bygel electrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3572] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 67-69 and ending at the stop codon found atnucleotide positions 1765-1767 (FIG. 26, SEQ ID NO:40). The predictedpolypeptide precursor is 566 amino acids long, has a calculatedmolecular weight of approximately 65,555 daltons and an estimated pI ofapproximately 5.44. Analysis of the full-length PRO710 sequence shown inFIG. 27 (SEQ ID NO:41) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 32, a transmembranedomain from about amino acid 454 to about amino acid 476, anaminoacyl-transfer RNA synthetase class-II signature sequence from aboutamino acid 6 to about amino acid 26 and potential N-glycosylation sitesfrom about amino acid 111 to about amino acid 114, from about amino acid146 to about amino acid 149 and from about amino acid 292 to about aminoacid 295. Clone DNA44161-1434 has been deposited with ATCC on May 27,1998 and is assigned ATCC deposit no. 209907.

[3573] Analysis of the amino acid sequence of the full-length PRO710polypeptide suggests that it possesses significant sequence similarityto the CDC45 protein, thereby indicating that PRO710 may be a novelCDC45 homolog. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO710 amino acid sequence and the following Dayhoff sequences,HSAJ3728_(—)1, CEF34D10_(—)1, S64939, UMU50276_(—)1, TRHY_SHEEP,CELT14E8_(—)1, RNA1_YEAST, LVU89340_(—)1, HSU80736_(—)1 andCEZK337_(—)2.

Example 15 Isolation of cDNA Clones Encoding Human PRO1151

[3574] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This consensussequence is herein designated DNA40665. Based on the DNA40665 consensussequence, oligonucleotides were synthesized: 1) to identify by PCR acDNA library that contained the sequence of interest, and 2) for use asprobes to isolate a clone of the full-length coding sequence forPRO1151.

[3575] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-CCAGACGCTGCTCTTCGAAAGGGTC-3′ (SEQ ID NO:48) reverse PCR primer5′-GGTCCCCGTAGGCCAGGTCCAGC-3′ (SEQ ID NO:49)

[3576] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA40665 sequence which had the followingnucleotide sequence hybridization probe5′-CTACTTCTTCAGCCTCAATGTGCACAGCTGGAATTACAAGGAGACGTACG-3′ (SEQ ID NO:50)

[3577] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO1151 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal kidneytissue.

[3578] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1151 (designated herein as DNA44694-1500[FIG. 29, SEQ ID NO:46]; and the derived protein sequence for PRO1151.

[3579] The entire nucleotide sequence of DNA44694-1500 is shown in FIG.29 (SEQ ID NO:46). Clone DNA44694-1500 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 272-274 and ending at the stop codon at nucleotide positions1049-1051 (FIG. 29). The predicted polypeptide precursor is 259 aminoacids long (FIG. 30). The full-length PRO1151 protein shown in FIG. 30has an estimated molecular weight of about 28,770 daltons and a pI ofabout 6.12. Analysis of the full-length PRO1151 sequence shown in FIG.30 (SEQ ID NO:47) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 20, a potentialN-glycosylation site from about amino acid 72 to about amino acid 75 andamino acid sequence blocks having homology to C1q domain-containingproteins from about amino acid 144 to about amino acid 178, from aboutamino acid 78 to about amino acid 111 and from about amino acid 84 toabout amino acid 117. Clone UNQ581 (DNA44694-1500) has been depositedwith ATCC on Aug. 11, 1998 and is assigned ATCC deposit no. 203114.

[3580] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 30 (SEQ ID NO:47), evidenced significant homologybetween the PRO1151 amino acid sequence and the following Dayhoffsequences: ACR3_HUMAN, HP25_TAMAS, HUMC1QB2_(—)1, P_R99306, CA1F_HUMAN,JX0369, CA24_HUMAN, S32436, P_R28916 and CA54_HUMAN.

Example 16 Isolation of cDNA Clones Encoding Human PRO1282

[3581] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This consensussequence is designated herein as DNA33778. Based on the DNA33778consensus sequence, oligonucleotides were synthesized: 1) to identify byPCR a cDNA library that contained the sequence of interest, and 2) foruse as probes to isolate a clone of the full-length coding sequence forPRO1282.

[3582] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′TCTTCAGCCGCTTGCGCAACCTC3′ (SEQ ID NO:53); and reverse PCRprimer 5′TTGCTCACATCCAGCTCCTGCAGG3′ (SEQ ID NO:54).

[3583] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA33778 sequence which had the followingnucleotide sequence: hybridization probe5′TGGATGTTGTCCAGACAACCAGCTGGAGCTGTATCCGAGGC3′ (SEQ ID NO:55).

[3584] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO1282 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal liver.

[3585] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1282 (designated herein as DNA45495-1550[FIG. 31, SEQ ID NO:51]; and the derived protein sequence for PRO1282.

[3586] The entire coding sequence of PRO1282 is shown in FIG. 31 (SEQ IDNO:51). Clone DNA45495-1550 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 120-122,and an apparent stop codon at nucleotide positions 2139-2141 (SEQ IDNO:51). The predicted polypeptide precursor is 673 amino acids long. Thesignal peptide is at about amino acids 1-23; the transmembrane domain isat about amino acids 579-599; an EGF-like domain cysteine patternsignature starts at about amino acid 430; and leucine zipper patternsstart at about amino acids 197 and 269 of SEQ ID NO:52, see FIG. 32.Clone DNA45495-1550 has been deposited with the ATCC and is assignedATCC deposit no. 203156. The full-length PRO1282 protein shown in FIG.32 has an estimated molecular weight of about 71,655 daltons and a pI ofabout 7.8.

[3587] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 32 (SEQ ID NO:52), revealed sequence identitybetween the PRO1282 amino acid sequence and the following Dayhoffsequences (data from database incorporated by reference): AB007876_(—)1,RNPLGPV_(—)1, MUSLRRP_(—)1, ALS_PAPPA, AC004142_(—)1, ALS_HUMAN,AB014462_(—)1, DMTARTAN_(—)1, HSCHON03_(—)1 and S46224.

Example 17 Isolation of cDNA Clones Encoding Human PRO358

[3588] Using the method described in Example 1 above, a single ESTsequence was identified in the Incyte database, designated herein asINC3115949. Based on the INC3115949 EST sequence, oligonucleotides weresynthesized to identify by PCR a cDNA library that contained thesequence of interest and for use as probes to isolate a clone of thefull-length coding sequence for PRO358.

[3589] A pair of PCR primers (forward and reverse) were synthesized:forward PCR primer 5′-TCCCACCAGGTATCATAAACTGAA-3′ (SEQ ID NO:58) reversePCR primer 5′-TTATAGACAATCTGTTCTCATCAGAGA-3′ (SEQ ID NO:59)

[3590] A probe was also synthesized:5′-AAAAAGCATACTTGGAATGGCCCAAGGATAGGTGTAAATG-3′ (SEQ ID NO:60)

[3591] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO358 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human bone marrow(LIB256). The cDNA libraries used to isolated the cDNA clones wereconstructed by standard methods using commercially available reagentssuch as those from Invitrogen, San Diego, Calif. The cDNA was primedwith oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3592] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO358 (FIG. 33, SEQ ID NO:56) and thederived protein sequence for PRO358 (FIGS. 34, SEQ ID NO:57).

[3593] The entire nucleotide sequence of the clone identified(DNA47361-1154) is shown in FIG. 33 (SEQ ID NO:56). Clone DNA47361-1154contains a single open reading frame with an apparent translationalinitiation site (ATG start signal) at nucleotide positions underlined inFIG. 33. The predicted polypeptide precursor is 811 amino acids long,including a putative signal sequence (amino acids 1 to 19), anextracellular domain (amino acids 20 to 575, including leucine richrepeats in the region from position 55 to position 575), a putativetransmembrane domain (amino acids 576 to 595). Clone DNA47361-1249 hasbeen deposited with ATCC and is assigned ATCC deposit no. 209431.

Example 18 Isolation of cDNA Clones Encoding Human PRO1310

[3594] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This consensussequence is designated herein as DNA37164. Based on the DNA37164consensus sequence, oligonucleotides were synthesized: 1) to identify byPCR a cDNA library that contained the sequence of interest, and 2) foruse as probes to isolate a clone of the full-length coding sequence forPRO1310.

[3595] PCR primers (forward and reverse) were synthesized: forward PCRprimer: 5′GTTCTCAATGAGCTACCCGTCCCC3′ (SEQ ID NO:63) and reverse PCRprimer: 5′CGCGATGTAGTGGAACTCGGGCTC3′ (SEQ ID NO:64).

[3596] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA47394 sequence which had the followingnucleotide sequence: hybridization probe:5′ATCCGCATAAACCCTCAGTCCTGGTTTGATAATGGGAGCATCTGCATGAG3′ (SEQ ID NO:65).

[3597] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO1310 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal livertissue.

[3598] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1310 and the derived protein sequencefor PRO1310.

[3599] The entire coding sequence of PRO1310 is shown in FIG. 35 (SEQ IDNO:61). Clone DNA47394-1572 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 326-328,and an apparent stop codon at nucleotide positions 2594-2596 (SEQ IDNO:61). The predicted polypeptide precursor is 765 amino acids long. Thesignal peptide is at about amino acids 1-25 of SEQ ID NO:62. CloneDNA47394-1572 has been deposited with ATCC and is assigned ATCC depositno. 203109. The full-length PRO1310 protein shown in FIG. 36 has anestimated molecular weight of about 85,898 daltons and a pI of about6.87.

[3600] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 36 (SEQ ID NO:62), revealed sequence identitybetween the PRO1310 amino acid sequence and the following Dayhoffsequences: AF017639_(—)1, P_W36817, JC5256, CBPH_HUMAN, MMU23184_(—)1,CBPN_HUMAN, HSU83411_(—)1, CEF01D4_(—)7, RNU62897_(—)1 and P_W11851.

Example 19 Isolation of cDNA Clones Encoding Human PRO698

[3601] A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA39906) is shown in FIG. 39 (SEQ ID NO:68). Based on theDNA39906 sequence shown in FIG. 39, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO698. In order to screen severallibraries for a full-length clone, DNA from the libraries was screenedby PCR amplification, as per Ausubel et al., Current Protocols inMolecular Biology, with the PCR primer pair. A positive library was thenused to isolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

[3602] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-AGCTGTGGTCATGGTGGTGTGGTG-3′ (SEQ ID NO:69) reverse PCR primer5′-CTACCTTGGCCATAGGTGATCCGC-3′ (SEQ ID NO:70)

[3603] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA39906 sequence which had the followingnucleotide sequence hybridization probe5′-CATCAGCAAACCGTCTGTGGTTCAGCTCAACTGGAGAGGGTT-3′ (SEQ ID NO:71)

[3604] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO698 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human bone marrowtissue (LIB255). The cDNA libraries used to isolate the cDNA clones wereconstructed by standard methods using commercially available reagentssuch as those from Invitrogen, San Diego, Calif. The cDNA was primedwith oligo dT containing a NotI site, linked with blunt to SalIhemikinased adaptors, cleaved with NotI, sized appropriately by gelelectrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3605] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 14-16 and ending at the stop codon found atnucleotide positions 1544-1546 (FIG. 37, SEQ ID NO:66). The predictedpolypeptide precursor is 510 amino acids long, has a calculatedmolecular weight of approximately 57,280 daltons and an estimated pI ofapproximately 5.61. Analysis of the full-length PRO698 sequence shown inFIG. 38 (SEQ ID NO:67) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 20, potentialN-glycosylation sites from about amino acid 72 to about amino acid 75,from about amino acid 136 to about amino acid 139, from about amino acid193 to about amino acid 196, from about amino acid 253 to about aminoacid 256, from about amino acid 352 to about amino acid 355 and fromabout amino acid 411 to about amino acid 414 an amino acid block havinghomology to legume lectin beta-chain proteins from about amino acid 20to about amino acid 39 and an amino acid block having homology to theHBGF/FGF family of proteins from about amino acid 338 to about aminoacid 365. Clone DNA48320-1433 has been deposited with ATCC on May 27,1998 and is assigned ATCC deposit no. 209904.

[3606] Analysis of the amino acid sequence of the full-length PRO698polypeptide suggests that it possesses significant sequence similarityto the olfactomedin protein, thereby indicating that PRO698 may be anovel olfactomedin homolog. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced significanthomology between the PRO698 amino acid sequence and the followingDayhoff sequences, OLFM_RANCA, I73637, AB006686S3_(—)1, RNU78105_(—)1,RNU72487_(—)1, P_R98225, CELC48E7_(—)4, CEF11C3_(—)3, XLU85970_(—)1 andS42257.

Example 20 Isolation of cDNA Clones Encoding Human PRO732

[3607] A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone whose sequence (hereindesignated as DNA42580) is shown in FIG. 45 (SEQ ID NO:77). The DNA42580sequence was then compared to a variety of known EST sequences toidentify homologies. The EST databases employed included public ESTdatabases (e.g., GenBank) and a proprietary EST DNA database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.). The search was performedusing the computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460480 (1996)) as a comparison to a 6 frame translationof the EST sequence. Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into consensus DNA sequences with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.).

[3608] Using the above analysis, a consensus DNA sequence was assembledrelative to other EST sequences using phrap. This consensus sequence isherein designated consen01. Proprietary Genentech EST sequences wereemployed in the consensus assembly and they are herein designatedDNA20239 (FIG. 42; SEQ ID NO:74), DNA38050 (FIG. 43; SEQ ID NO:75) andDNA40683 (FIG. 44; SEQ ID NO:76).

[3609] Based on the consen01 sequence, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO732. Forward and reverse PCR primersgenerally range from 20 to 30 nucleotides and are often designed to givea PCR product of about 100-1000 bp in length. The probe sequences aretypically 40-55 bp in length. In some cases, additional oligonucleotidesare synthesized when the consensus sequence is greater than about 1-1.5kbp. In order to screen several libraries for a full-length clone, DNAfrom the libraries was screened by PCR amplification, as per Ausubel etal., Current Protocols in Molecular Biology, with the PCR primer pair. Apositive library was then used to isolate clones encoding the gene ofinterest using the probe oligonucleotide and one of the primer pairs.

[3610] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-ATGTTTGTGTGGAAGTGCCCCG-3′ (SEQ ID NO:78) forward PCR primer5′-GTCAACATGCTCCTCTGC-3′ (SEQ ID NO:79) reverse PCR primer5′-AATCCATTGTGCACTGCAGCTCTAGG-3′ (SEQ ID NO:80) reverse PCR primer5′-GAGCATGCCACCACTGGACTGAC-3′ (SEQ ID NO:81)

[3611] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA44143 sequence which had the followingnucleotide sequence hybridization probe5′-GCCGATGCTGTCCTAGTGGAAACAACTCCACTGTAACTAGATTGATCTATGCAC-3′ (SEQ IDNO:82)

[3612] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pairs identified above. A positivelibrary was then used to isolate clones encoding the PRO732 gene usingthe probe oligonucleotide and one of the PCR primers.

[3613] RNA for construction of the cDNA libraries was isolated fromhuman fetal lung tissue (LIB26). The cDNA libraries used to isolate thecDNA clones were constructed by standard methods using commerciallyavailable reagents such as those from Invitrogen, San Diego, Calif. ThecDNA was primed with oligo dT containing a NotI site, linked with bluntto SalI hemikinased adaptors, cleaved with NotI, sized appropriately bygel electrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3614] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 88-90 and ending at the stop codon found atnucleotide positions 1447-1449 (FIG. 40, SEQ ID NO:72). The predictedpolypeptide precursor is 453 amino acids long, has a calculatedmolecular weight of approximately 50,419 daltons and an estimated pI ofapproximately 5.78. Analysis of the full-length PRO732 sequence shown inFIG. 41 (SEQ ID NO:73) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 28, transmembranedomains from about amino acid 37 to about amino acid 57, from aboutamino acid 93 to about amino acid 109, from about amino acid 126 toabout amino acid 148, from about amino acid 151 to about amino acid 172,from about amino acid 197 to about amino acid 215, from about amino acid231 to about amino acid 245, from about amino acid 260 to about aminoacid 279, from about amino acid 315 to about amino acid 333, from aboutamino acid 384 to about amino acid 403 and from about amino acid 422 toabout amino acid 447, potential N-glycosylation sites from about aminoacid 33 to about amino acid 36, from about amino acid 34 to about aminoacid 37, from about amino acid 179 to about amino acid 183, from aboutamino acid 298 to about amino acid 301, from about amino acid 337 toabout amino acid 340 and from about amino acid 406 to about amino acid409, an amino acid block having homology to the MIP family of proteinsfrom about amino acid 119 to about amino acid 149 and an amino acidblock having homology to DNA/RNA non-specific endonuclease proteins fromabout amino acid 279 to about amino acid 286. Clone DNA48334-1435 hasbeen deposited with ATCC on Jun. 2, 1998 and is assigned ATCC depositno. 209924.

[3615] Analysis of the amino acid sequence of the full-length PRO732polypeptide suggests that it possesses significant sequence similarityto the Diff33 protein, thereby indicating that PRO732 may be a novelDiff33 homolog. More specifically, an analysis of the Dayhoff database(version 35.45 SwissProt 35) evidenced significant homology between thePRO732 amino acid sequence and the following Dayhoff sequences,HS179M20_(—)2, MUSTETU_(—)1, CER11H6_(—)2, RATDRP_(—)1, S51256, E69226,AE000869_(—)1, JC4120, CYB_PARTE and P_R50619.

Example 21 Isolation of cDNA Clones Encoding Human PRO120

[3616] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This consensussequence is designated herein consen0352. The consen0352 sequence wasthen extended using repeated cycles of BLAST and phrap to extend theconsensus sequence as far as possible using the sources of EST sequencesdiscussed above. The extended consensus sequence is designated herein asDNA34365. Based on the DNA34365 consensus sequence, oligonucleotideswere synthesized: 1) to identify by PCR a cDNA library that containedthe sequence of interest, and 2) for use as probes to isolate a clone ofthe full-length coding sequence for PRO1120.

[3617] PCR primers (forward and reverse) were synthesized: forward PCRprimers: 5′-GAAGCCGGCTGTCTGAATC-3′ (SEQ ID NO:85),5′-GGCCAGCTATCTCCGCAG-3′ (SEQ ID NO:86), 5′-AAGGGCCTGCAAGAGAAG-3′ (SEQID NO:87), 5′-CACTGGGACAACTGTGGG-3′ (SEQ ID NO:88),5′-CAGAGGCAACGTGGAGAG-3′ (SEQ ID NO:89), and 5′-AAGTATTGTCATACAGTGTTC-3′(SEQ ID NO:90); reverse PCR primers: 5′-TAGTACTTGGGCACGAGGTTGGAG-3′ (SEQID NO:91), and 5′-TCATACCAACTGCTGGTCATTGGC-3′ (SEQ ID NO:92).

[3618] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA34365 consensus sequence which had the followingnucleotide sequence: hybridization probe:5′-CTCAAGCTGCTGGACACGGAGCGGCCGGTGAATCGGTTTCACTTG-3′ (SEQ ID NO:93).

[3619] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pairs identified above. A positivelibrary was then used to isolate clones encoding the PRO1120 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal kidneytissue.

[3620] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1120 (designated herein as DNA48606-1479[FIG. 46, SEQ ID NO:83]; and the derived protein sequence for PRO1120.

[3621] The entire coding sequence of PRO1120 is shown in FIG. 46 (SEQ IDNO:83). Clone DNA48606-1479 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 608-610and an apparent stop codon at nucleotide positions 3209-3211. Thepredicted polypeptide precursor is 867 amino acids long. The full-lengthPRO1120 protein shown in FIG. 47 has an estimated molecular weight ofabout 100,156 Daltons and a pI of about 9.44. Additional features of thePRO1120 polypeptide include a signal peptide at about amino acids 1-17;a sulfatase signature at about amino acids 86-98; regions of homology tosulfatases at about amino acids 87-106, 133-146, 216-229, 291-320, and365-375; and potential N-glycosylation sites at about amino acids 65-68,112-115, 132-135, 149-152, 171-174, 198-201, 241-245, 561-564, 608-611,717-720, 754-757, and 764-767.

[3622] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 47 (SEQ ID NO:84), revealed significant homologybetween the PRO1120 amino acid sequence and the following Dayhoffsequences: CELK09C4_(—)1, GL6S_HUMAN, G65169, NCU89492_(—)1,BCU44852_(—)1, E64903, P_R51355, STS_HUMAN, GA6S_HUMAN, and IDS_MOUSE.Clone DNA48606-1479 was deposited with the ATCC on Jul. 1, 1998, and isassigned ATCC deposit no. 203040.

Example 22 Isolation of cDNA Clones Encoding Human PRO537

[3623] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated as Incyte EST cluster no. 29605. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460-480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48350.

[3624] In light of an observed sequence homology between the DNA48350consensus sequence and an EST sequence encompassed within the Merck ESTclone no. R63443, the Merck EST clone R63443 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.48 and is herein designated as DNA49141-1431.

[3625] Clone DNA49141-1431 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 97-99 andending at the stop codon at nucleotide positions 442-444 (FIG. 48). Thepredicted polypeptide precursor is 115 amino acids long (FIG. 49). Thefull-length PRO537 protein shown in FIG. 49 has an estimated molecularweight of about 13,183 daltons and a pI of about 12.13. Analysis of thefull-length PRO537 sequence shown in FIG. 49 (SEQ ID NO:95) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 31, a potential N-glycosylation site from aboutamino acid 44 to about amino acid 47, potential N-myristolation sitesfrom about amino acid 3 to about amino acid 8 and from about amino acid16 to about amino acid 21 and an amino acid block having homology tomulticopper oxidase proteins from about amino acid 97 to about aminoacid 105. Clone DNA49141-1431 has been deposited with ATCC on Jun. 23,1998 and is assigned ATCC deposit no. 203003.

[3626] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 49 (SEQ ID NO:95), evidenced homology between thePRO537 amino acid sequence and the following Dayhoff sequences: A54523,CELF22H10_(—)2, FKH4_MOUSE, OTX1_HUMAN, URB1_USTMA, KNOB_PLAFN,A32895_(—)1, AF036332_(—)1, HRG_HUMAN and HRP3_PLAFS.

Example 23 Isolation of cDNA Clones Encoding Human PRO536

[3627] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as ss.clu2437.init. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460-480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48351.

[3628] In light of an observed sequence homology between the DNA48351consensus sequence and an EST sequence encompassed within the Merck ESTclone no. Hi 1129, the Merck EST clone Hi 1129 was purchased and thecDNA insert was obtained and sequenced. It was found that this insertencoded a full-length protein. The sequence of this cDNA insert is shownin FIG. 50 and is herein designated as DNA49142-1430.

[3629] Clone DNA49142-1430 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 48-50 andending at the stop codon at nucleotide positions 987-989 (FIG. 50). Thepredicted polypeptide precursor is 313 amino acids long (FIG. 51). Thefull-length PRO536 protein shown in FIG. 51 has an estimated molecularweight of about 34,189 daltons and a pI of about 4.8. Analysis of thefull-length PRO536 sequence shown in FIG. 51 (SEQ ID NO:97) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 25, a potential N-glycosylation site from aboutamino acid 45 to about amino acid 48 and an amino acid sequence blockhaving homology to sulfatase proteins from about amino acid 16 to aboutamino acid 26. Clone DNA49142-1430 has been deposited with ATCC on Jun.23, 1998 and is assigned ATCC deposit no. 203002.

[3630] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 51 (SEQ ID NO:97), evidenced homology between thePRO536 amino acid sequence and the following Dayhoff sequences:APU46857_(—)1, PK2_DICDI, H64743, F5I14_(—)18, CEAM_ECOLI, GEN14267,H64965, TCU39815_(—)1, PSBJ_ODOSI and P_R06980.

Example 24 Isolation of cDNA Clones Encoding Human PRO535

[3631] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as ss.clu12694.init. This EST clustersequence was then compared to a variety of expressed sequence tag (EST)databases which included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ®, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460480 (1996)). Those comparisons resulting ina BLAST score of 70 (or in some cases 90) or greater that did not encodeknown proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48352. Two propietary Genentech EST sequences wereemployed in the assembly are are herein shown in FIGS. 54 and 55.

[3632] In light of an observed sequence homology between the DNA48352consensus sequence and an EST sequence encompassed within the Merck ESTclone no. H86994, the Merck EST clone H86994 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.52 and is herein designated as DNA49143-1429.

[3633] Clone DNA49143-1429 contains a single open reading frame with anapparent translational initiation site at nucleotide positions 78-80 andending at the stop codon at nucleotide positions 681-683 (FIG. 52). Thepredicted polypeptide precursor is 201 amino acids long (FIG. 53). Thefull-length PRO535 protein shown in FIG. 53 has an estimated molecularweight of about 22,180 daltons and a pI of about 9.68. Analysis of thefull-length PRO535 sequence shown in FIG. 53 (SEQ ID NO:99) evidencesthe presence of the following: a signal peptide from about amino acid 1to about amino acid 25, a transmembrane domain from about amino acid 155to about amino acid 174, a potential N-glycosylation site from aboutamino acid 196 to about amino acid 199 and FKBP-type peptidyl-prolylcis-trans isomer signature sequences from about amino acid 62 to aboutamino acid 77, from about amino acid 87 to about amino acid 123 and fromabout amino acid 128 to about amino acid 141. Clone DNA49143-1429 hasbeen deposited with ATCC on Jun. 23, 1998 and is assigned ATCC depositno. 203013.

[3634] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-sequence alignment analysis of the full-length sequenceshown in FIG. 53 (SEQ ID NO:99), evidenced homology between the PRO535amino acid sequence and the following Dayhoff sequences: S71237,P_R93551, P_R28980, S71238, FKB2_HUMAN, CELC05C8_(—)1, S55383, S72485,CELC50F2_(—)6 and S75144.

Example 25 Isolation of cDNA Clones Encoding Human PRO718

[3635] A cDNA sequence isolated in the amylase screen described inExample 2 (human fetal lung library) above is herein designated DNA43512(see FIG. 62; SEQ ID NO:108). The DNA43512 sequence was then compared toa variety of expressed sequence tag (EST) databases which includedpublic EST databases (e.g., GenBank) and a proprietary EST DNA database(LIFESEQ™, Incyte Pharmaceuticals, Palo Alto, Calif.) to identifyexisting homologies. The homology search was performed using thecomputer program BLAST or BLAST2 (Altshul et ale, Methods in Enzymology266:460-480 (1996)). Those comparisons resulting in a BLAST score of 70(or in some cases 90) or greater that did not encode known proteins wereclustered and assembled into consensus DNA sequences with the program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained therefrom is herein designated DNA45625.Proprietary Genentech EST sequences were employed in the assembly andare herein shown in FIGS. 58-61.

[3636] Based on the DNA45625 sequence, oligonucleotide probes weregenerated and used to screen a human fetal lung library (LIB25) preparedas described in paragraph 1 of Example 2 above. The cloning vector waspRK5B (pRK5B is a precursor of pRK5D that does not contain the SfiIsite; see, Holmes et al., Science, 253:1278-1280 (1991)), and the cDNAsize cut was less than 2800 bp.

[3637] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-GGGTGGATGGTACTGCTGCATCC-3′ (SEQ ID NO:109) reverse PCR primer5′-TGTTGTGCTGTGGGAAATCAGATGTG-3′ (SEQ ID NO:110)

[3638] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA45625 sequence which had the followingnucleotide sequence: hybridization probe5′-GTGTCTGGAGGCTGTGGCCGTTTTGTTTTCTTGGGCTAAAATCGGG-3′ (SEQ ID NO:111)

[3639] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO718 gene usingthe probe oligonucleotide and one of the PCR primers.

[3640] A full length clone was identified that contained a single openreading frame with an apparent translational initiation site atnucleotide positions 36-38 and ending at the stop codon found atnucleotide positions 607-609 (FIG. 56; SEQ ID NO:102). The predictedpolypeptide precursor is 157 amino acids long, has a calculatedmolecular weight of approximately 17,400 daltons and an estimated pI ofapproximately 5.78. Analysis of the full-length PRO718 sequence shown inFIG. 57 (SEQ ID NO:103) evidences the presence of the following: a typeII transmembrane domain from about amino acid 21 to about amino acid 40,and other transmembrane domains at about amino acid 58 to about aminoacid 78, about amino acid 95 to about amino acid 114, and about aminoacid 127 to about amino acid 147; a cell attachment sequence from aboutamino acid 79 to about amino acid 81; and a potential N-glycosylationsite from about amino acid 53 to about amino acid 56. CloneDNA49647-1398 has been deposited with ATCC on Jun. 2, 1998 and isassigned ATCC deposit no. 209919.

[3641] Analysis of the amino acid sequence of the full-length PRO718polypeptide suggests that it possesses no significant sequencesimilarity to any known protein. However, an analysis of the Dayhoffdatabase (version 35.45 SwissProt 35) evidenced some degree of homologybetween the PRO718 amino acid sequence and the following Dayhoffsequences: AF045606_(—)1, AF039906_(—)1, SPBC8D2_(—)2, S63441, F64728,COX_TRYBB, F64375, E64173, RPYGJT_(—)3, MTCY261_(—)23.

Example 26 Isolation of cDNA Clones Encoding Human PRO872

[3642] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST sequence designated hereinas clu120709.init. The clu120709.init sequence was then compared aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.) to identify existing homologies. The homology search wasperformed using the computer program BLAST or BLAST2 (Altshul et al.,Methods in Enzymology 266:460-480 (1996)). Those comparisons resultingin a BLAST score of 70 (or in some cases 90) or greater that did notencode known proteins were clustered and assembled into a consensus DNAsequence with the program “phrap” (Phil Green, University of Washington,Seattle, Wash.). The consensus sequence obtained therefrom is hereindesignated DNA48254.

[3643] In light of an observed sequence homology between the DNA48254consensus sequence and an EST sequence encompassed within the Incyte ESTclone no. 3438068, the Incyte EST clone 3438068 was purchased and thecDNA insert was obtained and sequenced. It was found that this insertencoded a full-length protein. The sequence of this cDNA insert is shownin FIG. 63 and is the full-length DNA sequence for PRO872. CloneDNA49819-1439 was deposited with the ATCC on Jun. 2, 1998, and isassigned ATCC deposit no. 209931.

[3644] The entire nucleotide sequence of DNA49819-1439 is shown in FIG.63 (SEQ ID NO:112). Clone DNA49819-1439 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 14-16 and ending at the stop codon at nucleotide positions1844-1846 (FIG. 63). The predicted polypeptide precursor is 610 aminoacids long (FIG. 64). The full-length PRO872 protein shown in FIG. 64has an estimated molecular weight of about 66,820 daltons and a pI ofabout 8.65. Analysis of the full-length PRO872 sequence shown in FIG. 64(SEQ ID NO:113) evidences the presence of the following features: asignal peptide at amino acid 1 to about 18, putative transmembranedomains at about amino acids 70-87, 200-222 and 568-588; sequenceidentity with bacterial-type phytoene dehydrogenase protein at aboutamino acids 71-105; sequence identity with a regulator of chromosomecondensation (RCC1) signature 2 at about amino acids 201-211; leucinezipper patterns at about amino acids 214-235, 221-242, 228-249 and364-385; a potential N-glycosylation site at about amino acids 271-274;and a glycosaminoglycan attachment site at about amino acids 75-78.Analysis of the amino acid sequence of the full-length PRO872polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced homology between the PRO872 amino acid sequence and thefollowing Dayhoff sequences: PRCRTI_(—)1, S75951, S74689, CELF37C4_(—)3,CRTI_RHOCA, S76617, YNI2_METTL, MTV014_(—)14, AOFB_HUMAN, andMMU70429_(—)1.

Example 27 Isolation of cDNA Clones Encoding Human PRO1063

[3645] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of a single Incyte EST cluster sequencedesignated herein as ss.clu119743.init. The Incyte EST cluster sequencess.clu119743.init sequence was then compared to a variety of expressedsequence tag (EST) databases which included public EST databases (e.g.,GenBank) and a proprietary EST DNA database (LIFESEQ™, IncytePharmaceuticals, Palo Alto, Calif.) to identify existing homologies. Thehomology search was performed using the computer program BLAST or BLAST2(Altshul et al., Methods in Enzymology 266:460-480 (1996)). Thosecomparisons resulting in a BLAST score of 70 (or in some cases 90) orgreater that did not encode known proteins were clustered and assembledinto a consensus DNA sequence with the program “phrap” (Phil Green,University of Washington, Seattle, Wash.). The consensus sequenceobtained therefrom is herein designated DNA48288.

[3646] In light of an observed sequence homology between the DNA48288consensus sequence and an EST sequence encompassed within the Incyte ESTclone no. 2783726, the Incyte EST clone 2783726 was purchased and thecDNA insert was obtained and sequenced. It was found that this insertencoded a full-length protein. The sequence of this cDNA insert is shownin FIG. 65 and is herein designated DNA49820-1427.

[3647] The full length clone shown in FIG. 65 contained a single openreading frame with an apparent translational initiation site atnucleotide positions 90-92 and ending at the stop codon found atnucleotide positions 993-995 (FIG. 65; SEQ ID NO:114). The predictedpolypeptide precursor is 301 amino acids long, has a calculatedmolecular weight of approximately 33,530 daltons and an estimated pI ofapproximately 4.80. Analysis of the full-length PRO1063 sequence shownin FIG. 66 (SEQ ID NO:115) evidences the presence of the following: asignal peptide from about amino acid 1 to about amino acid 21, potentialN-glycosylation sites from about amino acid 195 to about amino acid 198,from about amino acid 217 to about amino acid 220 and from about aminoacid 272 to about amino acid 275, a glycosaminoglycan attachment sitefrom about amino acid 267 to about amino acid 270, a microbodiesC-terminal targeting signal site from about amino acid 299 to aboutamino acid 301, a type II fibronectin collagen-binding domain homologysequence from about amino acid 127 to about amino acid 168 and afructose-bisphosphate aldolase class II protein homology sequence fromabout amino acid 101 to about amino acid 118. Clone DNA49820-1427 hasbeen deposited with the ATCC on Jun. 2, 1998 and is assigned ATCCdeposit no. 209932.

[3648] Analysis of the amino acid sequence of the full-length PRO1063polypeptide suggests that it possesses sequence similarity to the humantype IV collagenase protein. More specifically, an analysis of theDayhoff database (version 35.45 SwissProt 35) evidenced some degree ofhomology between the PRO1063 amino acid sequence and the followingDayhoff sequences, S68303, CFU68533_(—)1, P_P91139, RNU65656_(—)1,PA2R_RABIT, MMU56734_(—)1, FINC_XENLA, A48925, P_R92778 and FA12_HUMAN.

Example 28 Isolation of cDNA Clones Encoding Human PRO619

[3649] Use of the signal sequence algorithm described in Example 3 aboveallowed identification of an EST cluster sequence from the Incytedatabase, designated herein as 88434. This EST cluster sequence was thencompared to a variety of expressed sequence tag (EST) databases whichincluded public EST databases (e.g., GenBank) and a proprietary EST DNAdatabase (LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.) toidentify existing homologies. The homology search was performed usingthe computer program BLAST or BLAST2 (Altshul et al., Methods inEnzymology 266:460480 (1996)). Those comparisons resulting in a BLASTscore of 70 (or in some cases 90) or greater that did not encode knownproteins were clustered and assembled into a consensus DNA sequence withthe program “phrap” (Phil Green, University of Washington, Seattle,Wash.).

[3650] In light of an observed sequence homology between the consensussequence and an EST sequence encompassed within the Incyte EST clone no.1656694, the Incyte EST clone 1656694 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.67 and is herein designated as DNA49821-1562.

[3651] The full length clone shown in FIG. 67 contained a single openreading frame with an apparent translational initiation site atnucleotide positions 81-83 and ending at the stop codon found atnucleotide positions 450-452 (FIG. 67; SEQ ID NO:116). The predictedpolypeptide precursor (FIG. 68, SEQ ID NO:117) is 123 amino acids longincluding a predicted signal peptide at about amino acids 1-20. PRO619has a calculated molecular weight of approximately 13,710 daltons and anestimated pI of approximately 5.19. Clone DNA49821-1562 was depositedwith the ATCC on Jun. 16, 1998 and is assigned ATCC deposit no. 209981.

[3652] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 68 (SEQ ID NO:117), revealed significant homologybetween the PRO619 amino acid sequence and the following Dayhoffsequences: S35302, D87009_(—)1, HSU93494_(—)1, HUMIGLAM5_(—)1,D86999_(—)2, HUMIGLYM1_(—)1, HUMIGLYMKE_(—)1, A29491_(—)1, A29498_(—)1,and VPR2_MOUSE.

Example 29 Isolation of cDNA Clones Encoding Human PRO943

[3653] A consensus DNA sequence encoding PRO943 was assembled relativeto other EST sequences using phrap as described in Example 1 above. Thisconsensus sequence was then extended using repeated cycles of BLAST andphrap to extend the consensus sequence as far as possible using thesources of EST sequences discussed above. The extended consensussequence is herein designated DNA36360. Based on the DNA36360 consensussequence, oligonucleotides were synthesized: 1) to identify by PCR acDNA library that contained the sequence of interest, and 2) for use asprobes to isolate a clone of the full-length coding sequence for PRO943.

[3654] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-CGAGATGACGCCGAGCCCCC-3′ (SEQ ID NO:120) reverse PCR primer5′-CGGTTCGACACGCGGCAGGTG-3′ (SEQ ID NO:121)

[3655] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA36360 sequence which had the followingnucleotide sequence hybridization probe5′-TGCTGCTCCTGCTGCCGCCGCTGCTGCTGGGGGCCTTCCCGCCGG-3′ (SEQ ID NO:122)

[3656] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO943 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal braintissue.

[3657] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO943 (designated herein as DNA52192-1369[FIG. 69, SEQ ID NO:118]) and the derived protein sequence for PRO943.

[3658] The entire nucleotide sequence of DNA52192-1369 is shown in FIG.69 (SEQ ID NO:118). Clone DNA52192-1369 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 150-152 and ending at the stop codon at nucleotide positions1662-1664 (FIG. 69). The predicted polypeptide precursor is 504 aminoacids long (FIG. 70). The full-length PRO943 protein shown in FIG. 70has an estimated molecular weight of about 54,537 daltons and a pI ofabout 10.04. Analysis of the full-length PRO943 sequence shown in FIG.70 (SEQ ID NO:119) evidences the presence of the following: a signalpeptide from about amino acid 1 to about amino acid 17, a transmembranedomain from about amino acid 376 to about amino acid 396, tyrosinekinase phosphorylation sites from about amino acid 212 to about aminoacid 219 and from about amino acid 329 to about amino acid 336,potential N-glycosylation sites from about amino acid 111 to about aminoacid 114, from about amino acid 231 to about amino acid 234, from aboutamino acid 255 to about amino acid 258 and from about amino acid 293 toabout amino acid 296 and an immunoglobulin and MHC protein sequencehomology block from about amino acid 219 to about amino acid 236. CloneDNA52192-1369 has been deposited with ATCC on Jul. 1, 1998 and isassigned ATCC deposit no. 203042.

[3659] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 70 (SEQ ID NO:119), evidenced significanthomology between the PRO943 amino acid sequence and the followingDayhoff sequences: B4915_(—)1, A39752, FGR1_XENLA, S38579,RATHBFGFRB_(—)1, TVHU2F, FGR2_MOUSE, CEK3_CHICK, P_R21080 andA27171_(—)1.

Example 30 Isolation of cDNA Clones Encoding Human PRO1188

[3660] A consensus DNA sequence was assembled relative to other ESTsequences using the program “phrap” as described in Example 1 above.This consensus sequence is designated herein as DNA45679. Based on theDNA45679 consensus sequence, oligonucleotides were synthesized: 1) toidentify by PCR a cDNA library that contained the sequence of interest,and 2) for use as probes to isolate a clone of the full-length codingsequence for PRO1188.

[3661] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-CTGGTGCCTCAACAGGGAGCAG-3′ (SEQ ID NO:125) reverse PCR primer5′-CCATTGTGCAGGTCAGGTCACAG-3′ (SEQ ID NO:126)

[3662] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA45679 sequence which had the followingnucleotide sequence: hybridization probe5′-CTGGAGCAAGTGCTCAGCTGCCTGTGGTCAGACTGGGGTC-3′ (SEQ ID NO:127)

[3663] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO1188 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal kidneytissue.

[3664] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1188 (designated herein as DNA52598-1518[FIG. 71, SEQ ID NO:123]); and the derived protein sequence for PRO1188.

[3665] The entire coding sequence of PRO1188 is shown in FIG. 71 (SEQ IDNO:123). Clone DNA52598-1518 contains a single open reading frame withan apparent translational initiation site at nucleotide positions136-138 and an apparent stop codon at nucleotide positions 3688-3690.The predicted polypeptide precursor is 1184 amino acids long. Thefull-length PRO1188 protein shown in FIG. 72 has an estimated molecularweight of about 132,582 Daltons and a pI of about 8.80. Additionalfeatures include: a signal peptide at about amino acids 1-31; an ATP/GTPbinding site motif A (P-loop) at about amino acids 266-273; an aldehydedehydrogenases cysteine active site at about amino acids 188-199; growthfactor and cytokines receptors family signature 2 at about amino acids153-159; and potential N-glycosylation sites at about amino acids129-132, 132-135, 346-349, 420423, 550-553, 631-634, 1000-1003, and1056-1059.

[3666] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 72 (SEQ ID NO:124), revealed significant homologybetween the PRO1188 amino acid sequence and the following Dayhoffsequences: SSU83114_(—)1, S56015, CET21B6_(—)4, CELT19D2_(—)1, andTSP1_MOUSE.

[3667] Clone DNA52598-1518 has been deposited with ATCC and is assignedATCC deposit no 203107.

Example 31 Isolation of cDNA Clones Encoding Human PRO1133

[3668] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. This sequence wasextended using repeated cycles of phrap. The extended consensus sequenceis designated herein DNA38102. Based on the DNA38102 consensus sequence,oligonucleotides were synthesized: 1) to identify by PCR a cDNA librarythat contained the sequence of interest, and 2) for use as probes toisolate a clone of the full-length coding sequence for PRO1133.

[3669] PCR primers (two forward and one reverse) were synthesized:forward PCR primer 1 5′-TCGATTATGGACGAACATGGCAGC-3′ (SEQ ID NO:130);forward PCR primer 2 5′-TTCTGAGATCCCTCATCCTC-3′ (SEQ ID NO:131); andreverse primer 5′-AGGTTCAGGGACAGCAAGTTTGGG-3′ (SEQ ID NO:132).

[3670] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consensus DNA38102 sequence which had the followingnucleotide sequence: hybridization probe5′TTTGCTGGACCTCGGCTACGGAATTGGCTTCCCTCTACGGACAGCTGGAT3′ (SEQ ID NO:133).

[3671] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with a PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO1133 gene usingthe probe oligonucleotide and one of the PCR primers. RNA forconstruction of the cDNA libraries was isolated from human fetal kidneytissue.

[3672] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO1133 and the derived protein sequencefor PRO1133.

[3673] The entire coding sequence of PRO1133 is shown in FIG. 73 (SEQ IDNO:128). Clone DNA53913-1490 contains a single open reading frame withan apparent translational initiation site at nucleotide positions266-268 and an apparent stop codon at nucleotide positions 1580-1582 ofSEQ ID NO:128. The predicted polypeptide precursor is 438 amino acidslong. The signal peptide is at amino acids 1-18 of SEQ ID NO:129.EGF-like domain cysteine pattern signatures start at 315 and 385 of SEQID NO:129 as shown in FIG. 74. Clone DNA53913-1490 has been depositedwith ATCC and is assigned ATCC deposit no. 203162. The full-lengthPRO1133 protein shown in FIG. 74 has an estimated molecular weight ofabout 49,260 daltons and a pI of about 6.15.

[3674] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 74 (SEQ ID NO:129), revealed some sequenceidentity between the PRO1133 amino acid sequence and the followingDayhoff sequences (data from the database incorporated herein):AF002717_(—)1, LMG1_HUMAN, B54665, UNC6_CAEEL, LML1_CAEEL, LMA5_MOUSE,MMU88353_(—)1, LMA1_HUMAN, HSLN2C64_(—)1 and AF005258_(—)1.

Example 32 Isolation of cDNA Clones Encoding Human PRO784

[3675] An initial DNA sequence (SEQ ID NO:136), referred to herein asDNA44661 and shown in FIG. 77, was identified using a yeast screen, in ahuman fetal lung cDNA library that preferentially represents the 5′ endsof the primary cDNA clones. DNA44661 was then compared to ESTs frompublic databases (e.g., GenBank), and a proprietary EST database(LIFESEQ®, Incyte Pharmaceuticals, Palo Alto, Calif.), using thecomputer program BLAST or BLAST2 [Altschul et al., Methods inEnzymology, 266:460-480 (1996)]. The ESTs were then clustered andassembled into a consensus DNA sequence using the computer program“phrap” (Phil Green, University of Washington, Seattle, Wash.). Theconsensus sequence obtained is designated herein as “DNA45463”. Based onthe DNA45463 consensus sequence, oligonucleotides were synthesized foruse as probes to isolate a clone of the full-length coding sequence forPRO784 from a human fetal lung cDNA library.

[3676] The full length DNA53978-1443 clone shown in FIG. 75 contained asingle open reading frame with an apparent translational initiation siteat nucleotide positions 37-39 and ending at the stop codon found atnucleotide positions 821-823 (FIG. 75; SEQ ID NO:134). The predictedpolypeptide precursor (FIG. 76, SEQ ID NO:135) is 228 amino acids long.PRO784 has a calculated molecular weight of approximately 25,735 Daltonsand an estimated pI of approximately 5.45. PRO784 has the followingfeatures: a signal peptide at about amino acid 1 to about 15;transmembrane domains at about amino acids 68 to about 87 and at about183 to about 204; potential N-myristoylation sites at about amino acids15-20, 51-56, 66-60, 163-168, and 206-211; and an RNP-1 proteinRNA-binding region at about amino acids 108 to about 117.

[3677] Clone DNA53978-1443 was deposited with ATCC on Jun. 16, 1998, andis assigned ATCC deposit no. 209983.

[3678] Based on a BLAST and FastA sequence alignment analysis (using theALIGN computer program) of the full-length sequence, PRO784 shows aminoacid sequence identity to the following proteins: RNU42209_(—)1,MMU91538_(—)1, CGU91742_(—)1, CELF55A4_(—)6, SC22_YEAST, and F48188.

Example 33 Isolation of cDNA Clones Encoding Human PRO783

[3679] A yeast screening assay was employed to identify cDNA clones thatencoded potential secreted proteins. Use of this yeast screening assayallowed identification of a single cDNA clone, designated herein asDNA45201 (FIG. 80; SEQ ID NO:139).

[3680] The DNA45201 sequence was then used to search expressed sequencetag (EST) databases for the presence of potential homologies. The ESTdatabases included public EST databases (e.g., GenBank) and aproprietary EST DNA database (LIFESEQ™, Incyte Pharmaceuticals, PaloAlto, Calif.). The search was performed using the computer program BLASTor BLAST2 (Altshul et al., Methods in Enzymology 266:460-480 (1996)).Those comparisons resulting in a BLAST score of 70 (or in some cases 90)or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, Univ. of Washington, Seattle, Wash.). The consensus sequenceobtained is herein designated as “consen01”. A proprietary Genentech ESTsequence was used in the consensus assembly and is herein designated asDNA14575 (FIG. 81; SEQ ID NO:140).

[3681] Based (n the consen01 sequence, oligonucleotides weresynthesized: 1) to identify by PCR a cDNA library that contained thesequence of interest, and 2) for use as probes to isolate a clone of thefull-length coding sequence for PRO783. In order to screen severallibraries for a full-length clone, DNA from the libraries was screenedby PCR amplification, as per Ausubel et al., Current Protocols inMolecular Biology, with the PCR primer pair. A positive library was thenused to isolate clones encoding the gene of interest using the probeoligonucleotide and one of the primer pairs.

[3682] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-GACTGTATCTGAGCCCCAGACTGC-3′ (SEQ ID NO:141), forward PCRprimer 5′-TCAGCAATGAGGTGCTGCTC-3′ (SEQ ID NO:142), and reverse PCRprimer 5′-TGAGGAAGATGAGGGACAGGTTGG-3′ (SEQ ID NO:143).

[3683] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the consen01 sequence which had the followingnucleotide sequence: hybridization probe5′-TATGGAAGCACCTGACTACGAAGTGCTATCCGTGCGAGAACAGCTATTCC-3′ (SEQ IDNO:144).

[3684] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with a PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO783 gene usingthe probe oligonucleotide and one of the PCR primers.

[3685] RNA for construction of the cDNA libraries was isolated fromhuman fetal kidney tissue (LIB228). The cDNA libraries used to isolatethe cDNA clones were constructed by standard methods using commerciallyavailable reagents such as those from Invitrogen, San Diego, Calif. ThecDNA was primed with oligo dT containing a NotI site, linked with bluntto SalI hemikinased adaptors, cleaved with NotI, sized appropriately bygel electrophoresis, and cloned in a defined orientation into a suitablecloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D thatdoes not contain the SfiI site; see, Holmes et al., Science,253:1278-1280 (1991)) in the unique XhoI and NotI sites.

[3686] DNA sequencing of the clones isolated as described above gave thefull-length DNA sequence for PRO783 [herein designated as DNA53996-1442](SEQ ID NO:137) and the derived protein sequence for PRO783.

[3687] The entire nucleotide sequence of DNA53996-1442 is shown in FIG.78 (SEQ ID NO:137). Clone DNA53996-1442 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 310-312 and ending at the stop codon at nucleotide positions1777-1779 (FIG. 78). The predicted polypeptide precursor is 489 aminoacids long (FIG. 79). The full-length PRO783 protein shown in FIG. 79has an estimated molecular weight of about 55,219 daltons and a pI ofabout 8.47. Analysis of the full-length PRO783 sequence shown in FIG. 79(SEQ ID NO:138) evidences the presence of the following features:transmembrane domains located at about amino acids 23-42, 67-89,111-135, 154-176, 194-218, 296-319,348-370,387-410 and 427-452; leucinezipper patterns located at about amino acids 263-283 and 399-420; apotential tyrosine kinase phosphorylation site at about amino acids180-187; potential N-glycosylation sites at about amino acids 105-108and 121-124; potential cAMP- and a cGMP-dependent protein kinasephosphorylation site at about amino acids 288-291; and a region havingsequence identity with bacterial rhodopsins retinal binding site proteinat about amino acids 190-218.

[3688] An analysis of the Dayhoff database (version 35.45 SwissProt 35)shows some sequence identity between the PRO783 amino acid sequence andthe following Dayhoff sequences: YNC2_CAEEL, D64048,ATAC002332_(—)3F4P9.3, NY2R_SHEEP, and VSH_MUMPA.

[3689] Clone DNA53996-1442 was deposited with the ATCC on Jun. 2, 1998,and is assigned ATCC deposit no. 209921.

Example 34 Isolation of cDNA Clones Encoding Human PRO820

[3690] An expressed sequence tag (EST) DNA database (Merck/Wash. U) wassearched and an EST designated EST no. AA504080, Merck clone 825136, wasidentified (library 312, human B-cell tonsil). Homology searchesrevealed that this EST showed sequence identity with low affinityimmunoglobulin gamma Fc receptor II. DNA sequencing gave the full-lengthDNA sequence for PRO820 and the derived protein sequence for PRO820.

[3691] The entire nucleotide sequence of DNA56041-1416 is shown in FIG.82 (SEQ ID NO:145). Clone DNA56041-1416 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 115-117 and ending at the stop codon at nucleotide positions487-489 (FIG. 82). The predicted polypeptide precursor is 124 aminoacids long (FIG. 83). The full-length PRO820 protein shown in FIG. 83has an estimated molecular weight of about 14,080 daltons and a pI ofabout 7.48. Clone DNA56041-1416 has been deposited with ATCC. Regardingthe sequence, it is understood that the deposited clone contains thecorrect sequence, and the sequences provided herein are based on knownsequencing techniques.

[3692] Still analyzing the amino acid sequence of SEQ ID NO:146, theputative signal peptide is at about amino acids 1-15 of SEQ ID NO:146.Protein kinase C phosphorylation sites are at about amino acids 20-22and 43-45 of SEQ ID NO:146. An N-myristoylation site is at about aminoacids 89-94 of SEQ ID NO:146. An immunoglobulin and majorhistocompatibility complex domain is at about amino acids 83-90 of SEQID NO:146. The corresponding nucleotides can be routinely determinedgiven the sequences provided herein.

Example 35 Isolation of cDNA Clones Encoding Human PRO1080

[3693] A consensus DNA sequence was assembled relative to other ESTsequences using phrap and was extended using repeated cycles of BLASTand phrap so as to extend the consensus sequence as far as possibleusing the sources of the EST sequences as described in Example 1 above.The consensus sequence is designated herein as DNA52640. An ESTproprietary to Genentech was employed in the consensus assembly and isherein designated as DNA36527 (FIG. 86; SEQ ID NO:149).

[3694] In light of an observed sequence homology between the DNA36527consensus sequence and an EST sequence encompassed within the Merck ESTclone no. 526423, the Merck EST clone 526423 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.84 and is herein designated as DNA56047-1456.

[3695] The entire nucleotide sequence of DNA56047-1456 is shown in FIG.84 (SEQ ID NO:147). Clone DNA56047-1456 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 159-161 and ending at the stop codon at nucleotide positions1233-1235 of SEQ ID NO:147 (FIG. 84). The predicted polypeptideprecursor is 358 amino acids long (FIG. 85). The full-length PRO1080protein shown in FIG. 85 has an estimated molecular weight of about40,514 daltons and a pI of about 6.08. Clone DNA56047-1456 has beendeposited with ATCC on Jun. 9, 1998. It is understood that the depositedclone has the actual nucleic acid sequence and that the sequencesprovided herein are based on known sequencing techniques.

[3696] Also shown in FIG. 85 are the approximate locations of the signalpeptide, cell attachment site, Nt-DnaJ domain signature, region havingsequence identity with Nt-DnaJ domain proteins, and N-glycosylationsites. The corresponding nucleic acids of these amino acid sequences andothers provided herein can be routinely determined by the informationprovided herein.

Example 36 Isolation of cDNA Clones Encoding Human PRO1079

[3697] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above, and is hereindesignated DNA52714. Based on information provided by the assembly, theclone for Merck EST no. H06898 was obtained and sequenced, therebygiving the nucleotide sequence designated herein as DNA56050-1455. Theentire nucleotide sequence of DNA56050-1455 is shown in FIG. 87 (SEQ IDNO:150). Clone DNA56050-1455 contains a single open reading frame withan apparent translational initiation site at nucleotide positions183-185 and ending at the stop codon at nucleotide positions 861-863(FIG. 87). The predicted polypeptide precursor is 226 amino acids long(FIG. 88). The full-length PRO1079 protein shown in FIG. 88 has anestimated molecular weight of about 24,611 Daltons and a pI of about4.85. Analysis of the full-length PRO1079 sequence shown in FIG. 88 (SEQID NO:3) evidences the presence of the following features: a signalpeptide at about amino acid 1-29; potential N-myristoylation sites atabout amino acids 10-15, and 51-56; homology to photosystem I psaG andpsakproteins at about amino acids 2 to 20; and homology to prolylendopeptidase family serine proteins at about amino acids 150 to 163.

[3698] Analysis of the amino acid sequence of the full-length PRO1079polypeptide using the Dayhoff database (version 35.45 SwissProt 35)evidenced some sequence identity between the PRO1079 amino acid sequenceand the following Dayhoff sequences: CEK10C3_(—)4, MMU50734_(—)1,D69503, AF051149_(—)1, and VSMP_CVMS.

[3699] Clone UNQ536 (DNA56050-1455) was deposited with the ATCC on Jun.22, 1998, and is assigned ATCC deposit no. 203011.

Example 37 Isolation of cDNA Clones Encoding Human PRO793

[3700] A cDNA clone (DNA56110-1437) encoding a native human PRO793polypeptide was identified by a yeast screen, in a human skin tumor cDNAlibrary that preferentially represents the 5′ ends of the primary cDNAclones. The yeast screen employed identified a single EST clonedesignated herein as DNA50177 (FIG. 91; SEQ ID NO:154). The DNA50177sequence was then compared to various EST databases including public ESTdatabases (e.g., GenBank), and a proprietary EST database (LIFESEQ®,Incyte Pharmaceuticals, Palo Alto, Calif.) to identify homologous ESTsequences. The comparison was performed using the computer program BLASTor BLAST2 [Altschul et al., Methods in Enzymology, 266:460-480 (1996)].Those comparisons resulting in a BLAST score of 70 (or in some cases,90) or greater that did not encode known proteins were clustered andassembled into a consensus DNA sequence with the program “phrap” (PhilGreen, University of Washington, Seattle, Wash.). This consensussequence is herein designated DNA50972.

[3701] In light of an observed sequence homology between the DNA50972consensus sequence and an EST sequence encompassed within the Merck ESTclone no. N33874, the Merck EST clone N33874 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.89 and is herein designated as DNA56110-1437.

[3702] The full-length DNA56110-1437 clone shown in FIG. 89 contains asingle open reading frame with an apparent translational initiation siteat nucleotide positions 77-79 and ending at the stop codon at nucleotidepositions 491-493 (FIG. 89). The predicted polypeptide precursor is 138amino acids long (FIG. 90). The full-length PRO793 protein shown in FIG.90 has an estimated molecular weight of about 15,426 daltons and a pI ofabout 10.67. Analysis of the full-length PRO793 sequence shown in FIG.90 (SEQ ID NO:153) evidences the presence of the following:transmembrane domains from about amino acid 12 to about amino acid 30,from about amino acid 33 to about amino acid 52, from about amino acid69 to about amino acid 89 and from about amino acid 93 to about aminoacid 109, potential N-myristolation sites from about amino acid 11 toabout amino acid 16, from about amino acid 51 to about amino acid 56 andfrom about amino acid 116 to about amino acid 121 and an amino acidsequence block having homology to an aminoacyl-transfer RNA synthetaseclass-II protein from about amino acid 49 to about amino acid 59. CloneDNA56110-1437 has been deposited with ATCC on Aug. 11, 1998 and isassigned ATCC deposit no. 203113.

[3703] An analysis of the Dayhoff database (version 35.45 SwissProt 35),using a WU-BLAST-2 sequence alignment analysis of the full-lengthsequence shown in FIG. 90 (SEQ ID NO:153), evidenced certain homologybetween the PRO793 amino acid sequence and the following Dayhoffsequences: S47453, AF015193_(—)12, MTEHGNS9_(—)2, E64030, H69784,D64995, CD53_MOUSE, GEN8006, AE001138_(—)7 and COX2_STRPU.

Example 38 Isolation of cDNA Clones Encoding Human PRO1016

[3704] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. The consensussequence obtained is herein designated DNA53502.

[3705] In light of an observed sequence homology between the DNA53502consensus sequence and an EST sequence encompassed within the Merck ESTclone no. 38680, the Merck EST clone 38680 was purchased and the cDNAinsert was obtained and sequenced. It was found that this insert encodeda full-length protein. The sequence of this cDNA insert is shown in FIG.92.

[3706] The entire nucleotide sequence of DNA56113-1378 is shown in FIG.92 (SEQ ID NO:155). Clone DNA56113-1378 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 168-170 and ending at the stop codon at nucleotide positions1302-1304 (FIG. 92). The predicted polypeptide precursor is 378 aminoacids long (FIG. 93). The full-length PRO1016 protein shown in FIG. 93has an estimated molecular weight of about 44,021 daltons and a pI ofabout 9.07. Clone DNA56113-1378 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

[3707] Analysis of the amino acid sequence of the full-length PRO1016polypeptide suggests that portions of it possess sequence identity withacyltransferase, thereby indicating that PRO1016 may be a novelacyltransferase.

[3708] Still analyzing the amino acid sequence of SEQ ID NO:156, theputative signal peptide is at about amino acids 1-18 of SEQ ID NO:156.The transmembrane domain(s) are at about amino acids 332-352 and 305-330of SEQ ID NO:156. The fructose-bisphosphate aldolase class-II proteinhomology sequence is at about amino acids 73-90 of SEQ ID NO:156. Theextradiol ring-cleavage dioxygenase protein is at about amino acids252-275 of SEQ ID NO:156. The corresponding nucleotides can be routinelydetermined given the sequences provided herein.

[3709] The specific Dayhoff database designation names of sequences towhich PRO1016 has sequence identity with include the following: S52645,P_R59712, P_R99249, P_R59713, BNAGPATRF_(—)1, CELT05H4_(—)15 andCELZK40_(—)1.

Example 39 Isolation of cDNA Encoding Human PRO1013

[3710] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. The consensus DNAsequence was then extended using repeated cycles of BLAST and phrap toextend the consensus sequence as far as possible using the sources ofEST sequences.

[3711] In light of an observed sequence homology between the consensussequence and an EST sequence encompassed within the Incyte EST clone no.3107695, the Incyte EST clone 3107695 was purchased and the cDNA insertwas obtained and sequenced. It was found that this insert encoded afull-length protein. The sequence of this cDNA insert is shown in FIG.94 and is herein designated as DNA56410-1414.

[3712] The entire nucleotide sequence of DNA56410-1414 is shown in FIG.94 (SEQ ID NO:157). Clone DNA56410-1414 contains a single open readingframe with an apparent translational initiation site at nucleotidepositions 17-19 and ending at the stop codon at nucleotide positions1244-1246 (FIG. 94). The predicted polypeptide precursor is 409 aminoacids long (FIG. 95). The full-length PRO1013 protein shown in FIG. 95has an estimated molecular weight of about 46,662 daltons and a pI ofabout 7.18. Clone DNA56410-1414 has been deposited with the ATCC.Regarding the sequence, it is understood that the deposited clonecontains the correct sequence, and the sequences provided herein arebased on known sequencing techniques.

[3713] Still analyzing the amino acid sequence of SEQ ID NO:158, theputative signal peptide is at about amino acids 1-19 of SEQ ID NO:158.N-glycosylation sites are at about amino acids 75-78 and 322-325 of SEQID NO:158. An N-myristoylation site is at about amino acids 184-189 ofSEQ ID NO:158. A growth factor and cytokine receptor family domain is atabout amino acids 134-149 of SEQ ID NO:158. The correspondingnucleotides can be routinely determined given the sequences providedherein.

[3714] Blast analysis showed some sequence identity with other proteins.Specifically, PRO1013 has some sequence identity with at least theDayhoff sequences designated: D63877_(—)1; MHU22019_(—)1,AE000730_(—)10, and AF019079_(—)1.

Example 40 Isolation of cDNA Clones Encoding Human PRO937

[3715] A consensus DNA sequence was assembled relative to other ESTsequences using phrap as described in Example 1 above. That consensussequence is herein designated DNA49651. Based on the DNA49651 consensussequence, oligonucleotides were synthesized: 1) to identify by PCR acDNA library that contained the sequence of interest, and 2) for use asprobes to isolate a clone of the full-length coding sequence for PRO937.

[3716] PCR primers (forward and reverse) were synthesized: forward PCRprimer 5′-CTCCGTGGTAAACCCCACAGCCC-3′ (SEQ ID NO:161); and reverse PCRprimer 5′-TCACATCGATGGGATCCATGACCG-3′ (SEQ ID NO:162).

[3717] Additionally, a synthetic oligonucleotide hybridization probe wasconstructed from the DNA48651 sequence which had the followingnucleotide sequence: hybridization probe5′-GGTCTCGTGACTGTGAAGCCATGTTACAACTACTGCTCAAACATCATGAG-3′ (SEQ IDNO:163).

[3718] In order to screen several libraries for a source of afull-length clone, DNA from the libraries was screened by PCRamplification with the PCR primer pair identified above. A positivelibrary was then used to isolate clones encoding the PRO937 gene usingthe probe oligonucleotide and one of the PCR primers.

0 SEQUENCE LISTING The patent application contains a lengthy “SequenceListing” section. A copy of the “Sequence Listing” is available inelectronic form from the USPTO web site(http://seqdata.uspto.gov/sequence.html?DocID=20030027162). Anelectronic copy of the “Sequence Listing” will also be available fromthe USPTO upon request and payment of the fee set forth in 37 CFR1.19(b)(3).

What is claimed is:
 1. Isolated nucleic acid having at least 80%sequence identity to a nucleotide sequence that encodes a polypeptidecomprising an amino acid sequence selected from the group consisting ofthe amino acid sequence shown in FIG. 2 (SEQ ID NO:2), FIG. 4 (SEQ IDNO:6), FIG. 6 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:14), FIG. 12 (SEQ IDNO:20), FIG. 15 (SEQ ID NO:23), FIG. 18 (SEQ ID NO:28), FIG. 20 (SEQ IDNO:30), FIG. 23 (SEQ ID NO:33), FIG. 25 (SEQ ID NO:36), FIG. 27 (SEQ IDNO:41), FIG. 30 (SEQ ID NO:47), FIG. 32 (SEQ ID NO:52), FIG. 34 (SEQ IDNO:57), FIG. 36 (SEQ ID NO:62), FIG. 38 (SEQ ID NO:67), FIG. 41 (SEQ IDNO:73), FIG. 47 (SEQ ID NO:84), FIG. 49 (SEQ ID NO:95), FIG. 51 (SEQ IDNO:97), FIG. 53 (SEQ ID NO:99), FIG. 57 (SEQ ID NO:103), FIG. 64 (SEQ IDNO:113), FIG. 66 (SEQ ID NO:115), FIG. 68 (SEQ ID NO:117), FIG. 70 (SEQID NO:119), FIG. 72 (SEQ ID NO:124), FIG. 74 (SEQ ID NO:129), FIG. 76(SEQ ID NO:135), FIG. 79 (SEQ ID NO:138), FIG. 83 (SEQ ID NO:146), FIG.85 (SEQ ID NO:148), FIG. 88 (SEQ ID NO:151), FIG. 90 (SEQ ID NO:153),FIG. 93 (SEQ ID NO:156), FIG. 95 (SEQ ID NO:158), FIG. 97 (SEQ IDNO:160), FIG. 99 (SEQ ID NO:165), FIG. 101 (SEQ ID NO:167), FIG. 103(SEQ ID NO:169), FIG. 105 (SEQ ID NO:171), FIG. 109 (SEQ ID NO:175),FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ ID NO:179), FIG. 115 (SEQ IDNO:181), FIG. 117 (SEQ ID NO:183), FIG. 120 (SEQ ID NO:189), FIG. 122(SEQ ID NO:194), FIG. 125 (SEQ ID NO:197), FIG. 127 (SEQ ID NO:199),FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ ID NO:203), FIG. 133 (SEQ IDNO:205), FIG. 135 (SEQ ID NO:207), FIG. 137 (SEQ ID NO:209), FIG. 139(SEQ ID NO:211), FIG. 141 (SEQ ID NO:213), FIG. 144 (SEQ ID NO:216),FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ ID NO:221), FIG. 151 (SEQ IDNO:223), FIG. 153 (SEQ ID NO:225), FIG. 155 (SEQ ID NO:227), FIG. 157(SEQ ID NO:229), FIG. 159 (SEQ ID NO:231), FIG. 161 (SEQ ID NO:236),FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ ID NO:246), FIG. 167 (SEQ IDNO:248), FIG. 169 (SEQ ID NO:250), FIG. 171 (SEQ ID NO:253), FIG. 174(SEQ ID NO:256), FIG. 176 (SEQ ID NO:258), FIG. 178 (SEQ ID NO:260),FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ ID NO:264), FIG. 184 (SEQ IDNO:266), FIG. 186 (SEQ ID NO:268), FIG. 188 (SEQ ID NO:270), FIG. 190(SEQ ID NO:272), FIG. 192 (SEQ ID NO:274), FIG. 194 (SEQ ID NO:276),FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ ID NO:281), FIG. 200 (SEQ IDNO:283), FIG. 202 (SEQ ID NO:285), FIG. 204 (SEQ ID NO:287), FIG. 206(SEQ ID NO:289), FIG. 208 (SEQ ID NO:291), FIG. 210 (SEQ ID NO:293),FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ ID NO:297), FIG. 216 (SEQ IDNO:299), FIG. 218 (SEQ ID NO:301), FIG. 220 (SEQ ID NO:303), FIG. 226(SEQ ID NO:309), FIG. 228 (SEQ ID NO:314), FIG. 230 (SEQ ID NO:319),FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ ID NO:334), FIG. 238 (SEQ IDNO:340), FIG. 240 (SEQ ID NO:345), FIG. 242 (SEQ ID NO:347), FIG. 244(SEQ ID NO:349), FIG. 246 (SEQ ID NO:351), FIG. 248 (SEQ ID NO:353),FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ ID NO:357), FIG. 254 (SEQ IDNO:359), FIG. 256 (SEQ ID NO:361), FIG. 258 (SEQ ID NO:363), FIG. 260(SEQ ID NO:365), FIG. 262 (SEQ ID NO:367), FIG. 264 (SEQ ID NO:369),FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ ID NO:373), FIG. 270 (SEQ IDNO:375), FIG. 272 (SEQ ID NO:377), FIG. 274 (SEQ ID NO:379), FIG. 276(SEQ ID NO:381), FIG. 278 (SEQ ID NO:387), FIG. 280 (SEQ ID NO:389),FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ ID NO:399), FIG. 286 (SEQ IDNO:401), FIG. 288 (SEQ ID NO:403), FIG. 290 (SEQ ID NO:408), FIG. 292(SEQ ID NO:410), FIG. 294 (SEQ ID NO:412), FIG. 296 (SEQ ID NO:414),FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ ID NO:418), FIG. 302 (SEQ IDNO:420), FIG. 304 (SEQ ID NO:422), FIG. 306 (SEQ ID NO:424), FIG. 308(SEQ ID NO:495), FIG. 310 (SEQ ID NO:497), FIG. 312 (SEQ ID NO:499),FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ ID NO:503), FIG. 318 (SEQ IDNO:505), FIG. 320 (SEQ ID NO:507), FIG. 322 (SEQ ID NO:509), FIG. 324(SEQ ID NO:511), FIG. 326 (SEQ ID NO:513), FIG. 328 (SEQ ID NO:515) andFIG. 330 (SEQ ID NO:517).
 2. The nucleic acid sequence of claim 1,wherein said nucleotide sequence comprises a nucleotide sequenceselected from the group consisting of the sequence shown in FIG. 1 (SEQID NO:1), FIG. 3 (SEQ ID NO:5), FIG. 5 (SEQ ID NO:7), FIG. 8 (SEQ IDNO:13), FIG. 11 (SEQ ID NO:19), FIG. 14 (SEQ ID NO:22), FIG. 17 (SEQ IDNO:27), FIG. 19 (SEQ ID NO:29), FIG. 22 (SEQ ID NO:32), FIG. 24 (SEQ IDNO:35), FIG. 26 (SEQ ID NO:40), FIG. 29 (SEQ ID NO:46), FIG. 31 (SEQ IDNO:51), FIG. 33 (SEQ ID NO:56), FIG. 35 (SEQ ID NO:61), FIG. 37 (SEQ IDNO:66), FIG. 40 (SEQ ID NO:72), FIG. 46 (SEQ ID NO:83), FIG. 48 (SEQ IDNO:94), FIG. 50 (SEQ ID NO:96), FIG. 52 (SEQ ID NO:98), FIG. 56 (SEQ IDNO:102), FIG. 63 (SEQ ID NO:112), FIG. 65 (SEQ ID NO:114), FIG. 67 (SEQID NO:116), FIG. 69 (SEQ ID NO:118), FIG. 71 (SEQ ID NO:123), FIG. 73(SEQ ID NO:128), FIG. 75 (SEQ ID NO:134), FIG. 78 (SEQ ID NO:137), FIG.82 (SEQ ID NO:145), FIG. 84 (SEQ ID NO:147), FIG. 87 (SEQ ID NO:150),FIG. 89 (SEQ ID NO:152), FIG. 92 (SEQ ID NO:155), FIG. 94 (SEQ IDNO:157), FIG. 96 (SEQ ID NO:159), FIG. 98 (SEQ ID NO:164), FIG. 100 (SEQID NO:166), FIG. 102 (SEQ ID NO:168), FIG. 104 (SEQ ID NO:170), FIG. 108(SEQ ID NO:174), FIG. 110 (SEQ ID NO:176), FIG. 112 (SEQ ID NO:178),FIG. 114 (SEQ ID NO:180), FIG. 116 (SEQ ID NO:182), FIG. 119 (SEQ IDNO:188), FIG. 121 (SEQ ID NO:193), FIG. 124 (SEQ ID NO:196), FIG. 126(SEQ ID NO:198), FIG. 128 (SEQ ID NO:200), FIG. 130 (SEQ ID NO:202),FIG. 132 (SEQ ID NO:204), FIG. 134 (SEQ ID NO:206), FIG. 136 (SEQ IDNO:208), FIG. 138 (SEQ ID NO:210), FIG. 140 (SEQ ID NO:212), FIG. 143(SEQ ID NO:215), FIG. 146 (SEQ ID NO:218), FIG. 148 (SEQ ID NO:220),FIG. 150 (SEQ ID NO:222), FIG. 152 (SEQ ID NO:224), FIG. 154 (SEQ IDNO:226), FIG. 156 (SEQ ID NO:228), FIG. 158 (SEQ ID NO:230), FIG. 160(SEQ ID NO:235), FIG. 162 (SEQ ID NO:240), FIG. 164 (SEQ ID NO:245),FIG. 166 (SEQ ID NO:247), FIG. 168 (SEQ ID NO:249), FIG. 170 (SEQ IDNO:252), FIG. 173 (SEQ ID NO:255), FIG. 175 (SEQ ID NO:257), FIG. 177(SEQ ID NO:259), FIG. 179 (SEQ ID NO:261), FIG. 181 (SEQ ID NO:263),FIG. 183 (SEQ ID NO:265), FIG. 185 (SEQ ID NO:267), FIG. 187 (SEQ IDNO:269), FIG. 189 (SEQ ID NO:271), FIG. 191 (SEQ ID NO:273), FIG. 193(SEQ ID NO:275), FIG. 195 (SEQ ID NO:277), FIG. 197 (SEQ ID NO:280),FIG. 199 (SEQ ID NO:282), FIG. 201 (SEQ ID NO:284), FIG. 203 (SEQ IDNO:286), FIG. 205 (SEQ ID NO:288), FIG. 207 (SEQ ID NO:290), FIG. 209(SEQ ID NO:292), FIG. 211 (SEQ ID NO:294), FIG. 213 (SEQ ID NO:296),FIG. 215 (SEQ ID NO:298), FIG. 217 (SEQ ID NO:300), FIG. 219 (SEQ IDNO:302), FIG. 225 (SEQ ID NO:308), FIG. 227 (SEQ ID NO:313), FIG. 229(SEQ ID NO:318), FIG. 232 (SEQ ID NO:325), FIG. 234 (SEQ ID NO:333),FIG. 237 (SEQ ID NO:339), FIG. 239 (SEQ ID NO:344), FIG. 241 (SEQ IDNO:346), FIG. 243 (SEQ ID NO:348), FIG. 245 (SEQ ID NO:350), FIG. 247(SEQ ID NO:352), FIG. 249 (SEQ ID NO:354), FIG. 251 (SEQ ID NO:356),FIG. 253 (SEQ ID NO:358), FIG. 255 (SEQ ID NO:360), FIG. 257 (SEQ IDNO:362), FIG. 259 (SEQ ID NO:364), FIG. 261 (SEQ ID NO:366), FIG. 263(SEQ ID NO:368), FIG. 265 (SEQ ID NO:370), FIG. 267 (SEQ ID NO:372),FIG. 269 (SEQ ID NO:374), FIG. 271 (SEQ ID NO:376), FIG. 273 (SEQ IDNO:378), FIG. 275 (SEQ ID NO:380), FIG. 277 (SEQ ID NO:386), FIG. 279(SEQ ID NO:388), FIG. 281 (SEQ ID NO:393), FIG. 283 (SEQ ID NO:398),FIG. 285 (SEQ ID NO:400), FIG. 287 (SEQ ID NO:402), FIG. 289 (SEQ IDNO:407), FIG. 291 (SEQ ID NO:409), FIG. 293 (SEQ ID NO:411), FIG. 295(SEQ ID NO:413), FIG. 297 (SEQ ID NO:415), FIG. 299 (SEQ ID NO:417),FIG. 301 (SEQ ID NO:419), FIG. 303 (SEQ ID NO:421), FIG. 305 (SEQ IDNO:423), FIG. 307 (SEQ ID NO:494), FIG. 309 (SEQ ID NO:496), FIG. 311(SEQ ID NO:498), FIG. 313 (SEQ ID NO:500), FIG. 315 (SEQ ID NO:502),FIG. 317 (SEQ ID NO:504), FIG. 319 (SEQ ID NO:506), FIG. 321 (SEQ IDNO:508), FIG. 323 (SEQ ID NO:510), FIG. 325 (SEQ ID NO:512), FIG. 327(SEQ ID NO:514) and FIG. 329 (SEQ ID NO:516).
 3. The nucleic acid ofclaim 1, wherein said nucleotide sequence comprises a nucleotidesequence selected from the group consisting of the full-length codingsequence of the sequence shown in FIG. 1 (SEQ ID NO:1), FIG. 3 (SEQ IDNO:5), FIG. 5 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:13), FIG. 11 (SEQ IDNO:19), FIG. 14 (SEQ ID NO:22), FIG. 17 (SEQ ID NO:27), FIG. 19 (SEQ IDNO:29), FIG. 22 (SEQ ID NO:32), FIG. 24 (SEQ ID NO:35), FIG. 26 (SEQ IDNO:40), FIG. 29 (SEQ ID NO:46), FIG. 31 (SEQ ID NO:51), FIG. 33 (SEQ IDNO:56), FIG. 35 (SEQ ID NO:61), FIG. 37 (SEQ ID NO:66), FIG. 40 (SEQ IDNO:72), FIG. 46 (SEQ ID NO:83), FIG. 48 (SEQ ID NO:94), FIG. 50 (SEQ IDNO:96), FIG. 52 (SEQ ID NO:98), FIG. 56 (SEQ ID NO:102), FIG. 63 (SEQ IDNO:112), FIG. 65 (SEQ ID NO:114), FIG. 67 (SEQ ID NO:116), FIG. 69 (SEQID NO:118), FIG. 71 (SEQ ID NO:123), FIG. 73 (SEQ ID NO:128), FIG. 75(SEQ ID NO:134), FIG. 78 (SEQ ID NO:137), FIG. 82 (SEQ ID NO:145), FIG.84 (SEQ ID NO:147), FIG. 87 (SEQ ID NO:150), FIG. 89 (SEQ ID NO:152),FIG. 92 (SEQ ID NO:155), FIG. 94 (SEQ ID NO:157), FIG. 96 (SEQ IDNO:159), FIG. 98 (SEQ ID NO:164), FIG. 100 (SEQ ID NO:166), FIG. 102(SEQ ID NO:168), FIG. 104 (SEQ ID NO:170), FIG. 108 (SEQ ID NO:174),FIG. 110 (SEQ ID NO:176), FIG. 112 (SEQ ID NO:178), FIG. 114 (SEQ IDNO:180), FIG. 116 (SEQ ID NO:182), FIG. 119 (SEQ ID NO:188), FIG. 121(SEQ ID NO:193), FIG. 124 (SEQ ID NO:196), FIG. 126 (SEQ ID NO:198),FIG. 128 (SEQ ID NO:200), FIG. 130 (SEQ ID NO:202), FIG. 132 (SEQ IDNO:204), FIG. 134 (SEQ ID NO:206), FIG. 136 (SEQ ID NO:208), FIG. 138(SEQ ID NO:210), FIG. 140 (SEQ ID NO:212), FIG. 143 (SEQ ID NO:215),FIG. 146 (SEQ ID NO:218), FIG. 148 (SEQ ID NO:220), FIG. 150 (SEQ IDNO:222), FIG. 152 (SEQ ID NO:224), FIG. 154 (SEQ ID NO:226), FIG. 156(SEQ ID NO:228), FIG. 158 (SEQ ID NO:230), FIG. 160 (SEQ ID NO:235),FIG. 162 (SEQ ID NO:240), FIG. 164 (SEQ ID NO:245), FIG. 166 (SEQ IDNO:247), FIG. 168 (SEQ ID NO:249), FIG. 170 (SEQ ID NO:252), FIG. 173(SEQ ID NO:255), FIG. 175 (SEQ ID NO:257), FIG. 177 (SEQ ID NO:259),FIG. 179 (SEQ ID NO:261), FIG. 181 (SEQ ID NO:263), FIG. 183 (SEQ IDNO:265), FIG. 185 (SEQ ID NO:267), FIG. 187 (SEQ ID NO:269), FIG. 189(SEQ ID NO:271), FIG. 191 (SEQ ID NO:273), FIG. 193 (SEQ ID NO:275),FIG. 195 (SEQ ID NO:277), FIG. 197 (SEQ ID NO:280), FIG. 199 (SEQ IDNO:282), FIG. 201 (SEQ ID NO:284), FIG. 203 (SEQ ID NO:286), FIG. 205(SEQ ID NO:288), FIG. 207 (SEQ ID NO:290), FIG. 209 (SEQ ID NO:292),FIG. 211 (SEQ ID NO:294), FIG. 213 (SEQ ID NO:296), FIG. 215 (SEQ IDNO:298), FIG. 217 (SEQ ID NO:300), FIG. 219 (SEQ ID NO:302), FIG. 225(SEQ ID NO:308), FIG. 227 (SEQ ID NO:313), FIG. 229 (SEQ ID NO:318),FIG. 232 (SEQ ID NO:325), FIG. 234 (SEQ ID NO:333), FIG. 237 (SEQ IDNO:339), FIG. 239 (SEQ ID NO:344), FIG. 241 (SEQ ID NO:346), FIG. 243(SEQ ID NO:348), FIG. 245 (SEQ ID NO:350), FIG. 247 (SEQ ID NO:352),FIG. 249 (SEQ ID NO:354), FIG. 251 (SEQ ID NO:356), FIG. 253 (SEQ IDNO:358), FIG. 255 (SEQ ID NO:360), FIG. 257 (SEQ ID NO:362), FIG. 259(SEQ ID NO:364), FIG. 261 (SEQ ID NO:366), FIG. 263 (SEQ ID NO:368),FIG. 265 (SEQ ID NO:370), FIG. 267 (SEQ ID NO:372), FIG. 269 (SEQ IDNO:374), FIG. 271 (SEQ ID NO:376), FIG. 273 (SEQ ID NO:378), FIG. 275(SEQ ID NO:380), FIG. 277 (SEQ ID NO:386), FIG. 279 (SEQ ID NO:388),FIG. 281 (SEQ ID NO:393), FIG. 283 (SEQ ID NO:398), FIG. 285 (SEQ IDNO:400), FIG. 287 (SEQ ID NO:402), FIG. 289 (SEQ ID NO:407), FIG. 291(SEQ ID NO:409), FIG. 293 (SEQ ID NO:411), FIG. 295 (SEQ ID NO:413),FIG. 297 (SEQ ID NO:415), FIG. 299 (SEQ ID NO:417), FIG. 301 (SEQ IDNO:419), FIG. 303 (SEQ ID NO:421), FIG. 305 (SEQ ID NO:423), FIG. 307(SEQ ID NO:494), FIG. 309 (SEQ ID NO:496), FIG. 311 (SEQ ID NO:498),FIG. 313 (SEQ ID NO:500), FIG. 315 (SEQ ID NO:502), FIG. 317 (SEQ IDNO:504), FIG. 319 (SEQ ID NO:506), FIG. 321 (SEQ ID NO:508), FIG. 323(SEQ ID NO:510), FIG. 325 (SEQ ID NO:512), FIG. 327 (SEQ ID NO:514) andFIG. 329 (SEQ ID NO:516).
 4. Isolated nucleic acid which comprises thefull-length coding sequence of the DNA deposited under any ATCCaccession number shown in Table
 10. 5. A vector comprising the nucleicacid of claim
 1. 6. The vector of claim 5 operably linked to controlsequences recognized by a host cell transformed with the vector.
 7. Ahost cell comprising the vector of claim
 5. 8. The host cell of claim 7wherein said cell is a CHO cell.
 9. The host cell of claim 7 whereinsaid cell is an E. coli.
 10. The host cell of claim 7 wherein said cellis a yeast cell.
 11. A process for producing a PRO polypeptidescomprising culturing the host cell of claim 7 under conditions suitablefor expression of said PRO polypeptide and recovering said PROpolypeptide from the cell culture.
 12. Isolated PRO polypeptide havingat least 80% sequence identity to an amino acid sequence selected fromthe group consisting of the amino acid sequence shown in FIG. 2 (SEQ IDNO:2), FIG. 4 (SEQ ID NO:6), FIG. 6 (SEQ ID NO:8), FIG. 9 (SEQ IDNO:14), FIG. 12 (SEQ ID NO:20), FIG. 15 (SEQ ID NO:23), FIG. 18 (SEQ IDNO:28), FIG. 20 (SEQ ID NO:30), FIG. 23 (SEQ ID NO:33), FIG. 25 (SEQ IDNO:36), FIG. 27 (SEQ ID NO:41), FIG. 30 (SEQ ID NO:47), FIG. 32 (SEQ IDNO:52), FIG. 34 (SEQ ID NO:57), FIG. 36 (SEQ ID NO:62), FIG. 38 (SEQ IDNO:67), FIG. 41 (SEQ ID NO:73), FIG. 47 (SEQ ID NO:84), FIG. 49 (SEQ IDNO:95), FIG. 51 (SEQ ID NO:97), FIG. 53 (SEQ ID NO:99), FIG. 57 (SEQ IDNO:103), FIG. 64 (SEQ ID NO:113), FIG. 66 (SEQ ID NO:115), FIG. 68 (SEQID NO:117), FIG. 70 (SEQ ID NO:119), FIG. 72 (SEQ ID NO:124), FIG. 74(SEQ ID NO:129), FIG. 76 (SEQ ID NO:135), FIG. 79 (SEQ ID NO:138), FIG.83 (SEQ ID NO:146), FIG. 85 (SEQ ID NO:148), FIG. 88 (SEQ ID NO:151),FIG. 90 (SEQ ID NO:153), FIG. 93 (SEQ ID NO:156), FIG. 95 (SEQ IDNO:158), FIG. 97 (SEQ ID NO:160), FIG. 99 (SEQ ID NO:165), FIG. 101 (SEQID NO:167), FIG. 103 (SEQ ID NO:169), FIG. 105 (SEQ ID NO:171), FIG. 109(SEQ ID NO:175), FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ ID NO:179),FIG. 115 (SEQ ID NO:181), FIG. 117 (SEQ ID NO:183), FIG. 120 (SEQ IDNO:189), FIG. 122 (SEQ ID NO:194), FIG. 125 (SEQ ID NO:197), FIG. 127(SEQ ID NO:199), FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ ID NO:203),FIG. 133 (SEQ ID NO:205), FIG. 135 (SEQ ID NO:207), FIG. 137 (SEQ IDNO:209), FIG. 139 (SEQ ID NO:211), FIG. 141 (SEQ ID NO:213), FIG. 144(SEQ ID NO:216), FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ ID NO:221),FIG. 151 (SEQ ID NO:223), FIG. 153 (SEQ ID NO:225), FIG. 155 (SEQ IDNO:227), FIG. 157 (SEQ ID NO:229), FIG. 159 (SEQ ID NO:231), FIG. 161(SEQ ID NO:236), FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ ID NO:246),FIG. 167 (SEQ ID NO:248), FIG. 169 (SEQ ID NO:250), FIG. 171 (SEQ IDNO:253), FIG. 174 (SEQ ID NO:256), FIG. 176 (SEQ ID NO:258), FIG. 178(SEQ ID NO:260), FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ ID NO:264),FIG. 184 (SEQ ID NO:266), FIG. 186 (SEQ ID NO:268), FIG. 188 (SEQ IDNO:270), FIG. 190 (SEQ ID NO:272), FIG. 192 (SEQ ID NO:274), FIG. 194(SEQ ID NO:276), FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ ID NO:281),FIG. 200 (SEQ ID NO:283), FIG. 202 (SEQ ID NO:285), FIG. 204 (SEQ IDNO:287), FIG. 206 (SEQ ID NO:289), FIG. 208 (SEQ ID NO:291), FIG. 210(SEQ ID NO:293), FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ ID NO:297),FIG. 216 (SEQ ID NO:299), FIG. 218 (SEQ ID NO:301), FIG. 220 (SEQ IDNO:303), FIG. 226 (SEQ ID NO:309), FIG. 228 (SEQ ID NO:314), FIG. 230(SEQ ID NO:319), FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ ID NO:334),FIG. 238 (SEQ ID NO:340), FIG. 240 (SEQ ID NO:345), FIG. 242 (SEQ IDNO:347), FIG. 244 (SEQ ID NO:349), FIG. 246 (SEQ ID NO:351), FIG. 248(SEQ ID NO:353), FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ ID NO:357),FIG. 254 (SEQ ID NO:359), FIG. 256 (SEQ ID NO:361), FIG. 258 (SEQ IDNO:363), FIG. 260 (SEQ ID NO:365), FIG. 262 (SEQ ID NO:367), FIG. 264(SEQ ID NO:369), FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ ID NO:373),FIG. 270 (SEQ ID NO:375), FIG. 272 (SEQ ID NO:377), FIG. 274 (SEQ IDNO:379), FIG. 276 (SEQ ID NO:381), FIG. 278 (SEQ ID NO:387), FIG. 280(SEQ ID NO:389), FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ ID NO:399),FIG. 286 (SEQ ID NO:401), FIG. 288 (SEQ ID NO:403), FIG. 290 (SEQ IDNO:408), FIG. 292 (SEQ ID NO:410), FIG. 294 (SEQ ID NO:412), FIG. 296(SEQ ID NO:414), FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ ID NO:418),FIG. 302 (SEQ ID NO:420), FIG. 304 (SEQ ID NO:422), FIG. 306 (SEQ IDNO:424), FIG. 308 (SEQ ID NO:495), FIG. 310 (SEQ ID NO:497), FIG. 312(SEQ ID NO:499), FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ ID NO:503),FIG. 318 (SEQ ID NO:505), FIG. 320 (SEQ ID NO:507), FIG. 322 (SEQ IDNO:509), FIG. 324 (SEQ ID NO:511), FIG. 326 (SEQ ID NO:513), FIG. 328(SEQ ID NO:515) and FIG. 330 (SEQ ID NO:517).
 13. Isolated PROpolypeptide having at least 80% sequence identity to the amino acidsequence encoded by a nucleic acid molecule deposited under any ATCCaccession number shown in Table
 10. 14. A chimeric molecule comprising apolypeptide according to claim 12 fused to a heterologous amino acidsequence.
 15. The chimeric molecule of claim 14 wherein saidheterologous amino acid sequence is an epitope tag sequence.
 16. Thechimeric molecule of claim 14 wherein said heterologous amino acidsequence is a Fc region of an immunoglobulin.
 17. An antibody whichspecifically binds to a PRO polypeptide according to claim
 12. 18. Theantibody of claim 17 wherein said antibody is a monoclonal antibody. 19.The antibody of claim 17 wherein said antibody is a humanized antibody.20. The antibody of claim 17 wherein said antibody is an antibodyfragment.
 21. An isolated nucleic acid molecule which has at least 80%sequence identity to a nucleic acid which comprises a nucleotidesequence selected from the group consisting of that shown in FIG. 1 (SEQID NO:1), FIG. 3 (SEQ ID NO:5), FIG. 5 (SEQ ID NO:7), FIG. 8 (SEQ IDNO:13), FIG. 11 (SEQ ID NO:19), FIG. 14 (SEQ ID NO:22), FIG. 17 (SEQ IDNO:27), FIG. 19 (SEQ ID NO:29), FIG. 22 (SEQ ID NO:32), FIG. 24 (SEQ IDNO:35), FIG. 26 (SEQ ID NO:40), FIG. 29 (SEQ ID NO:46), FIG. 31 (SEQ IDNO:51), FIG. 33 (SEQ ID NO:56), FIG. 35 (SEQ ID NO:61), FIG. 37 (SEQ IDNO:66), FIG. 40 (SEQ ID NO:72), FIG. 46 (SEQ ID NO:83), FIG. 48 (SEQ IDNO:94), FIG. 50 (SEQ ID NO:96), FIG. 52 (SEQ ID NO:98), FIG. 56 (SEQ IDNO:102), FIG. 63 (SEQ ID NO:112), FIG. 65 (SEQ ID NO:114), FIG. 67 (SEQID NO:116), FIG. 69 (SEQ ID NO:118), FIG. 71 (SEQ ID NO:123), FIG. 73(SEQ ID NO:128), FIG. 75 (SEQ ID NO:134), FIG. 78 (SEQ ID NO:137), FIG.82 (SEQ ID NO:145), FIG. 84 (SEQ ID NO:147), FIG. 87 (SEQ ID NO:150),FIG. 89 (SEQ ID NO:152), FIG. 92 (SEQ ID NO:155), FIG. 94 (SEQ IDNO:157), FIG. 96 (SEQ ID NO:159), FIG. 98 (SEQ ID NO:164), FIG. 100 (SEQID NO:166), FIG. 102 (SEQ ID NO:168), FIG. 104 (SEQ ID NO:170), FIG. 108(SEQ ID NO:174), FIG. 110 (SEQ ID NO:176), FIG. 112 (SEQ ID NO:178),FIG. 114 (SEQ ID NO:180), FIG. 116 (SEQ ID NO:182), FIG. 119 (SEQ IDNO:188), FIG. 121 (SEQ ID NO:193), FIG. 124 (SEQ ID NO:196), FIG. 126(SEQ ID NO:198), FIG. 128 (SEQ ID NO:200), FIG. 130 (SEQ ID NO:202),FIG. 132 (SEQ ID NO:204), FIG. 134 (SEQ ID NO:206), FIG. 136 (SEQ IDNO:208), FIG. 138 (SEQ ID NO:210), FIG. 140 (SEQ ID NO:212), FIG. 143(SEQ ID NO:215), FIG. 146 (SEQ ID NO:218), FIG. 148 (SEQ ID NO:220),FIG. 150 (SEQ ID NO:222), FIG. 152 (SEQ ID NO:224), FIG. 154 (SEQ IDNO:226), FIG. 156 (SEQ ID NO:228), FIG. 158 (SEQ ID NO:230), FIG. 160(SEQ ID NO:235), FIG. 162 (SEQ ID NO:240), FIG. 164 (SEQ ID NO:245),FIG. 166 (SEQ ID NO:247), FIG. 168 (SEQ ID NO:249), FIG. 170 (SEQ IDNO:252), FIG. 173 (SEQ ID NO:255), FIG. 175 (SEQ ID NO:257), FIG. 177(SEQ ID NO:259), FIG. 179 (SEQ ID NO:261), FIG. 181 (SEQ ID NO:263),FIG. 183 (SEQ ID NO:265), FIG. 185 (SEQ ID NO:267), FIG. 187 (SEQ IDNO:269), FIG. 189 (SEQ ID NO:271), FIG. 191 (SEQ ID NO:273), FIG. 193(SEQ ID NO:275), FIG. 195 (SEQ ID NO:277), FIG. 197 (SEQ ID NO:280),FIG. 199 (SEQ ID NO:282), FIG. 201 (SEQ ID NO:284), FIG. 203 (SEQ IDNO:286), FIG. 205 (SEQ ID NO:288), FIG. 207 (SEQ ID NO:290), FIG. 209(SEQ ID NO:292), FIG. 211 (SEQ ID NO:294), FIG. 213 (SEQ ID NO:296),FIG. 215 (SEQ ID NO:298), FIG. 217 (SEQ ID NO:300), FIG. 219 (SEQ IDNO:302), FIG. 225 (SEQ ID NO:308), FIG. 227 (SEQ ID NO:313), FIG. 229(SEQ ID NO:318), FIG. 232 (SEQ ID NO:325), FIG. 234 (SEQ ID NO:333),FIG. 237 (SEQ ID NO:339), FIG. 239 (SEQ ID NO:344), FIG. 241 (SEQ IDNO:346), FIG. 243 (SEQ ID NO:348), FIG. 245 (SEQ ID NO:350), FIG. 247(SEQ ID NO:352), FIG. 249 (SEQ ID NO:354), FIG. 251 (SEQ ID NO:356),FIG. 253 (SEQ ID NO:358), FIG. 255 (SEQ ID NO:360), FIG. 257 (SEQ IDNO:362), FIG. 259 (SEQ ID NO:364), FIG. 261 (SEQ ID NO:366), FIG. 263(SEQ ID NO:368), FIG. 265 (SEQ ID NO:370), FIG. 267 (SEQ ID NO:372),FIG. 269 (SEQ ID NO:374), FIG. 271 (SEQ ID NO:376), FIG. 273 (SEQ IDNO:378), FIG. 275 (SEQ ID NO:380), FIG. 277 (SEQ ID NO:386), FIG. 279(SEQ ID NO:388), FIG. 281 (SEQ ID NO:393), FIG. 283 (SEQ ID NO:398),FIG. 285 (SEQ ID NO:400), FIG. 287 (SEQ ID NO:402), FIG. 289 (SEQ IDNO:407), FIG. 291 (SEQ ID NO:409), FIG. 293 (SEQ ID NO:411), FIG. 295(SEQ ID NO:413), FIG. 297 (SEQ ID NO:415), FIG. 299 (SEQ ID NO:417),FIG. 301 (SEQ ID NO:419), FIG. 303 (SEQ ID NO:421), FIG. 305 (SEQ IDNO:423), FIG. 307 (SEQ ID NO:494), FIG. 309 (SEQ ID NO:496), FIG. 311(SEQ ID NO:498), FIG. 313 (SEQ ID NO:500), FIG. 315 (SEQ ID NO:502),FIG. 317 (SEQ ID NO:504), FIG. 319 (SEQ ID NO:506), FIG. 321 (SEQ IDNO:508), FIG. 323 (SEQ ID NO:510), FIG. 325 (SEQ ID NO:512), FIG. 327(SEQ ID NO:514) and FIG. 329 (SEQ ID NO:516).
 22. An isolated nucleicacid molecule which has at least 80% sequence identity to thefull-length coding sequence of a nucleotide sequence selected from thegroup consisting of that shown in FIG. 1 (SEQ ID NO:1), FIG. 3 (SEQ IDNO:5), FIG. 5 (SEQ ID NO:7), FIG. 8 (SEQ ID NO:13), FIG. 11 (SEQ IDNO:19), FIG. 14 (SEQ ID NO:22), FIG. 17 (SEQ ID NO:27), FIG. 19 (SEQ IDNO:29), FIG. 22 (SEQ ID NO:32), FIG. 24 (SEQ ID NO:35), FIG. 26 (SEQ IDNO:40), FIG. 29 (SEQ ID NO:46), FIG. 31 (SEQ ID NO:51), FIG. 33 (SEQ IDNO:56), FIG. 35 (SEQ ID NO:61), FIG. 37 (SEQ ID NO:66), FIG. 40 (SEQ IDNO:72), FIG. 46 (SEQ ID NO:83), FIG. 48 (SEQ ID NO:94), FIG. 50 (SEQ IDNO:96), FIG. 52 (SEQ ID NO:98), FIG. 56 (SEQ ID NO:102), FIG. 63 (SEQ IDNO:112), FIG. 65 (SEQ ID NO:114), FIG. 67 (SEQ ID NO:116), FIG. 69 (SEQID NO:118), FIG. 71 (SEQ ID NO:123), FIG. 73 (SEQ ID NO:128), FIG. 75(SEQ ID NO:134), FIG. 78 (SEQ ID NO:137), FIG. 82 (SEQ ID NO:145), FIG.84 (SEQ ID NO:147), FIG. 87 (SEQ ID NO:150), FIG. 89 (SEQ ID NO:152),FIG. 92 (SEQ ID NO:155), FIG. 94 (SEQ ID NO:157), FIG. 96 (SEQ IDNO:159), FIG. 98 (SEQ ID NO:164), FIG. 100 (SEQ ID NO:166), FIG. 102(SEQ ID NO:168), FIG. 104 (SEQ ID NO:170), FIG. 108 (SEQ ID NO:174),FIG. 110 (SEQ ID NO:176), FIG. 112 (SEQ ID NO:178), FIG. 114 (SEQ IDNO:180), FIG. 116 (SEQ ID NO:182), FIG. 119 (SEQ ID NO:188), FIG. 121(SEQ ID NO:193), FIG. 124 (SEQ ID NO:196), FIG. 126 (SEQ ID NO:198),FIG. 128 (SEQ ID NO:200), FIG. 130 (SEQ ID NO:202), FIG. 132 (SEQ IDNO:204), FIG. 134 (SEQ ID NO:206), FIG. 136 (SEQ ID NO:208), FIG. 138(SEQ ID NO:210), FIG. 140 (SEQ ID NO:212), FIG. 143 (SEQ ID NO:215),FIG. 146 (SEQ ID NO:218), FIG. 148 (SEQ ID NO:220), FIG. 150 (SEQ IDNO:222), FIG. 152 (SEQ ID NO:224), FIG. 154 (SEQ ID NO:226), FIG. 156(SEQ ID NO:228), FIG. 158 (SEQ ID NO:230), FIG. 160 (SEQ ID NO:235),FIG. 162 (SEQ ID NO:240), FIG. 164 (SEQ ID NO:245), FIG. 166 (SEQ IDNO:247), FIG. 168 (SEQ ID NO:249), FIG. 170 (SEQ ID NO:252), FIG. 173(SEQ ID NO:255), FIG. 175 (SEQ ID NO:257), FIG. 177 (SEQ ID NO:259),FIG. 179 (SEQ ID NO:261), FIG. 181 (SEQ ID NO:263), FIG. 183 (SEQ IDNO:265), FIG. 185 (SEQ ID NO:267), FIG. 187 (SEQ ID NO:269), FIG. 189(SEQ ID NO:271), FIG. 191 (SEQ ID NO:273), FIG. 193 (SEQ ID NO:275),FIG. 195 (SEQ ID NO:277), FIG. 197 (SEQ ID NO:280), FIG. 199 (SEQ IDNO:282), FIG. 201 (SEQ ID NO:284), FIG. 203 (SEQ ID NO:286), FIG. 205(SEQ ID NO:288), FIG. 207 (SEQ ID NO:290), FIG. 209 (SEQ ID NO:292),FIG. 211 (SEQ ID NO:294), FIG. 213 (SEQ ID NO:296), FIG. 215 (SEQ IDNO:298), FIG. 217 (SEQ ID NO:300), FIG. 219 (SEQ ID NO:302), FIG. 225(SEQ ID NO:308), FIG. 227 (SEQ ID NO:313), FIG. 229 (SEQ ID NO:318),FIG. 232 (SEQ ID NO:325), FIG. 234 (SEQ ID NO:333), FIG. 237 (SEQ IDNO:339), FIG. 239 (SEQ ID NO:344), FIG. 241 (SEQ ID NO:346), FIG. 243(SEQ ID NO:348), FIG. 245 (SEQ ID NO:350), FIG. 247 (SEQ ID NO:352),FIG. 249 (SEQ ID NO:354), FIG. 251 (SEQ ID NO:356), FIG. 253 (SEQ IDNO:358), FIG. 255 (SEQ ID NO:360), FIG. 257 (SEQ ID NO:362), FIG. 259(SEQ ID NO:364), FIG. 261 (SEQ ID NO:366), FIG. 263 (SEQ ID NO:368),FIG. 265 (SEQ ID NO:370), FIG. 267 (SEQ ID NO:372), FIG. 269 (SEQ IDNO:374), FIG. 271 (SEQ ID NO:376), FIG. 273 (SEQ ID NO:378), FIG. 275(SEQ ID NO:380), FIG. 277 (SEQ ID NO:386), FIG. 279 (SEQ ID NO:388),FIG. 281 (SEQ ID NO:393), FIG. 283 (SEQ ID NO:398), FIG. 285 (SEQ IDNO:400), FIG. 287 (SEQ ID NO:402), FIG. 289 (SEQ ID NO:407), FIG. 291(SEQ ID NO:409), FIG. 293 (SEQ ID NO:411), FIG. 295 (SEQ ID NO:413),FIG. 297 (SEQ ID NO:415), FIG. 299 (SEQ ID NO:417), FIG. 301 (SEQ IDNO:419), FIG. 303 (SEQ ID NO:421), FIG. 305 (SEQ ID NO:423), FIG. 307(SEQ ID NO:494), FIG. 309 (SEQ ID NO:496), FIG. 311 (SEQ ID NO:498),FIG. 313 (SEQ ID NO:500), FIG. 315 (SEQ ID NO:502), FIG. 317 (SEQ IDNO:504), FIG. 319 (SEQ ID NO:506), FIG. 321 (SEQ ID NO:508), FIG. 323(SEQ ID NO:510), FIG. 325 (SEQ ID NO:512), FIG. 327 (SEQ ID NO:514) andFIG. 329 (SEQ ID NO:516).
 23. An isolated extracellular domain of of PROpolypeptide.
 24. An isolated PRO polypeptide lacking its associatedsignal peptide.
 25. An isolated polypeptide having at least about 80%amino acid sequence identity to an extracellular domain of of PROpolypeptide.
 26. An isolated polypeptide having at least about 80% aminoacid sequence identity to a PRO polypeptide lacking its associatedsignal peptide.
 27. Isolated nucleic acid having at least 80% nucleicacid sequence identity to: (a) a nucleotide sequence encoding thepolypeptide shown in FIG. 2 (SEQ ID NO:2), FIG. 4 (SEQ ID NO:6), FIG. 6(SEQ ID NO:8), FIG. 9 (SEQ ID NO:14), FIG. 12 (SEQ ID NO:20), FIG. 15(SEQ ID NO:23), FIG. 18 (SEQ ID NO:28), FIG. 20 (SEQ ID NO:30), FIG. 23(SEQ ID NO:33), FIG. 25 (SEQ ID NO:36), FIG. 27 (SEQ ID NO:41), FIG. 30(SEQ ID NO:47), FIG. 32 (SEQ ID NO:52), FIG. 34 (SEQ ID NO:57), FIG. 36(SEQ ID NO:62), FIG. 38 (SEQ ID NO:67), FIG. 41 (SEQ ID NO:73), FIG. 47(SEQ ID NO:84), FIG. 49 (SEQ ID NO:95), FIG. 51 (SEQ ID NO:97), FIG. 53(SEQ ID NO:99), FIG. 57 (SEQ ID NO:103), FIG. 64 (SEQ ID NO:113), FIG.66 (SEQ ID NO:115), FIG. 68 (SEQ ID NO:117), FIG. 70 (SEQ ID NO:119),FIG. 72 (SEQ ID NO:124), FIG. 74 (SEQ ID NO:129), FIG. 76 (SEQ IDNO:135), FIG. 79 (SEQ ID NO:138), FIG. 83 (SEQ ID NO:146), FIG. 85 (SEQID NO:148), FIG. 88 (SEQ ID NO:151), FIG. 90 (SEQ ID NO:153), FIG. 93(SEQ ID NO:156), FIG. 95 (SEQ ID NO:158), FIG. 97 (SEQ ID NO:160), FIG.99 (SEQ ID NO:165), FIG. 101 (SEQ ID NO:167), FIG. 103 (SEQ ID NO:169),FIG. 105 (SEQ ID NO:171), FIG. 109 (SEQ ID NO:175), FIG. 111 (SEQ IDNO:177), FIG. 113 (SEQ ID NO:179), FIG. 115 (SEQ ID NO:181), FIG. 117(SEQ ID NO:183), FIG. 120 (SEQ ID NO:189), FIG. 122 (SEQ ID NO:194),FIG. 125 (SEQ ID NO:197), FIG. 127 (SEQ ID NO:199), FIG. 129 (SEQ IDNO:201), FIG. 131 (SEQ ID NO:203), FIG. 133 (SEQ ID NO:205), FIG. 135(SEQ ID NO:207), FIG. 137 (SEQ ID NO:209), FIG. 139 (SEQ ID NO:211),FIG. 141 (SEQ ID NO:213), FIG. 144 (SEQ ID NO:216), FIG. 147 (SEQ IDNO:219), FIG. 149 (SEQ ID NO:221), FIG. 151 (SEQ ID NO:223), FIG. 153(SEQ ID NO:225), FIG. 155 (SEQ ID NO:227), FIG. 157 (SEQ ID NO:229),FIG. 159 (SEQ ID NO:231), FIG. 161 (SEQ ID NO:236), FIG. 163 (SEQ IDNO:241), FIG. 165 (SEQ ID NO:246), FIG. 167 (SEQ ID NO:248), FIG. 169(SEQ ID NO:250), FIG. 171 (SEQ ID NO:253), FIG. 174 (SEQ ID NO:256),FIG. 176 (SEQ ID NO:258), FIG. 178 (SEQ ID NO:260), FIG. 180 (SEQ IDNO:262), FIG. 182 (SEQ ID NO:264), FIG. 184 (SEQ ID NO:266), FIG. 186(SEQ ID NO:268), FIG. 188 (SEQ ID NO:270), FIG. 190 (SEQ ID NO:272),FIG. 192 (SEQ ID NO:274), FIG. 194 (SEQ ID NO:276), FIG. 196 (SEQ IDNO:278), FIG. 198 (SEQ ID NO:281), FIG. 200 (SEQ ID NO:283), FIG. 202(SEQ ID NO:285), FIG. 204 (SEQ ID NO:287), FIG. 206 (SEQ ID NO:289),FIG. 208 (SEQ ID NO:291), FIG. 210 (SEQ ID NO:293), FIG. 212 (SEQ IDNO:295), FIG. 214 (SEQ ID NO:297), FIG. 216 (SEQ ID NO:299), FIG. 218(SEQ ID NO:301), FIG. 220 (SEQ ID NO:303), FIG. 226 (SEQ ID NO:309),FIG. 228 (SEQ ID NO:314), FIG. 230 (SEQ ID NO:319), FIG. 233 (SEQ IDNO:326), FIG. 235 (SEQ ID NO:334), FIG. 238 (SEQ ID NO:340), FIG. 240(SEQ ID NO:345), FIG. 242 (SEQ ID NO:347), FIG. 244 (SEQ ID NO:349),FIG. 246 (SEQ ID NO:351), FIG. 248 (SEQ ID NO:353), FIG. 250 (SEQ IDNO:355), FIG. 252 (SEQ ID NO:357), FIG. 254 (SEQ ID NO:359), FIG. 256(SEQ ID NO:361), FIG. 258 (SEQ ID NO:363), FIG. 260 (SEQ ID NO:365),FIG. 262 (SEQ ID NO:367), FIG. 264 (SEQ ID NO:369), FIG. 266 (SEQ IDNO:371), FIG. 268 (SEQ ID NO:373), FIG. 270 (SEQ ID NO:375), FIG. 272(SEQ ID NO:377), FIG. 274 (SEQ ID NO:379), FIG. 276 (SEQ ID NO:381),FIG. 278 (SEQ ID NO:387), FIG. 280 (SEQ ID NO:389), FIG. 282 (SEQ IDNO:394), FIG. 284 (SEQ ID NO:399), FIG. 286 (SEQ ID NO:401), FIG. 288(SEQ ID NO:403), FIG. 290 (SEQ ID NO:408), FIG. 292 (SEQ ID NO:410),FIG. 294 (SEQ ID NO:412), FIG. 296 (SEQ ID NO:414), FIG. 298 (SEQ IDNO:416), FIG. 300 (SEQ ID NO:418), FIG. 302 (SEQ ID NO:420), FIG. 304(SEQ ID NO:422), FIG. 306 (SEQ ID NO:424), FIG. 308 (SEQ ID NO:495),FIG. 310 (SEQ ID NO:497), FIG. 312 (SEQ ID NO:499), FIG. 314 (SEQ IDNO:501), FIG. 316 (SEQ ID NO:503), FIG. 318 (SEQ ID NO:505), FIG. 320(SEQ ID NO:507), FIG. 322 (SEQ ID NO:509), FIG. 324 (SEQ ID NO:511),FIG. 326 (SEQ ID NO:513), FIG. 328 (SEQ ID NO:515) or FIG. 330 (SEQ IDNO:517), lacking its associated signal peptide; (b) a nucleotidesequence encoding an extracellular domain of the polypeptide shown inFIG. 2 (SEQ ID NO:2), FIG. 4 (SEQ ID NO:6), FIG. 6 (SEQ ID NO:8), FIG. 9(SEQ ID NO:14), FIG. 12 (SEQ ID NO:20), FIG. 15 (SEQ ID NO:23), FIG. 18(SEQ ID NO:28), FIG. 20 (SEQ ID NO:30), FIG. 23 (SEQ ID NO:33), FIG. 25(SEQ ID NO:36), FIG. 27 (SEQ ID NO:41), FIG. 30 (SEQ ID NO:47), FIG. 32(SEQ ID NO:52), FIG. 34 (SEQ ID NO:57), FIG. 36 (SEQ ID NO:62), FIG. 38(SEQ ID NO:67), FIG. 41 (SEQ ID NO:73), FIG. 47 (SEQ ID NO:84), FIG. 49(SEQ ID NO:95), FIG. 51 (SEQ ID NO:97), FIG. 53 (SEQ ID NO:99), FIG. 57(SEQ ID NO:103), FIG. 64 (SEQ ID NO:113), FIG. 66 (SEQ ID NO:115), FIG.68 (SEQ ID NO:117), FIG. 70 (SEQ ID NO:119), FIG. 72 (SEQ ID NO:124),FIG. 74 (SEQ ID NO:129), FIG. 76 (SEQ ID NO:135), FIG. 79 (SEQ IDNO:138), FIG. 83 (SEQ ID NO:146), FIG. 85 (SEQ ID NO:148), FIG. 88 (SEQID NO:151), FIG. 90 (SEQ ID NO:153), FIG. 93 (SEQ ID NO:156), FIG. 95(SEQ ID NO:158), FIG. 97 (SEQ ID NO:160), FIG. 99 (SEQ ID NO:165), FIG.101 (SEQ ID NO:167), FIG. 103 (SEQ ID NO:169), FIG. 105 (SEQ ID NO:171),FIG. 109 (SEQ ID NO:175), FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ IDNO:179), FIG. 115 (SEQ ID NO:181), FIG. 117 (SEQ ID NO:183), FIG. 120(SEQ ID NO:189), FIG. 122 (SEQ ID NO:194), FIG. 125 (SEQ ID NO:197),FIG. 127 (SEQ ID NO:199), FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ IDNO:203), FIG. 133 (SEQ ID NO:205), FIG. 135 (SEQ ID NO:207), FIG. 137(SEQ ID NO:209), FIG. 139 (SEQ ID NO:211), FIG. 141 (SEQ ID NO:213),FIG. 144 (SEQ ID NO:216), FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ IDNO:221), FIG. 151 (SEQ ID NO:223), FIG. 153 (SEQ ID NO:225), FIG. 155(SEQ ID NO:227), FIG. 157 (SEQ ID NO:229), FIG. 159 (SEQ ID NO:231),FIG. 161 (SEQ ID NO:236), FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ IDNO:246), FIG. 167 (SEQ ID NO:248), FIG. 169 (SEQ ID NO:250), FIG. 171(SEQ ID NO:253), FIG. 174 (SEQ ID NO:256), FIG. 176 (SEQ ID NO:258),FIG. 178 (SEQ ID NO:260), FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ IDNO:264), FIG. 184 (SEQ ID NO:266), FIG. 186 (SEQ ID NO:268), FIG. 188(SEQ ID NO:270), FIG. 190 (SEQ ID NO:272), FIG. 192 (SEQ ID NO:274),FIG. 194 (SEQ ID NO:276), FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ IDNO:281), FIG. 200 (SEQ ID NO:283), FIG. 202 (SEQ ID NO:285), FIG. 204(SEQ ID NO:287), FIG. 206 (SEQ ID NO:289), FIG. 208 (SEQ ID NO:291),FIG. 210 (SEQ ID NO:293), FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ IDNO:297), FIG. 216 (SEQ ID NO:299), FIG. 218 (SEQ ID NO:301), FIG. 220(SEQ ID NO:303), FIG. 226 (SEQ ID NO:309), FIG. 228 (SEQ ID NO:314),FIG. 230 (SEQ ID NO:319), FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ IDNO:334), FIG. 238 (SEQ ID NO:340), FIG. 240 (SEQ ID NO:345), FIG. 242(SEQ ID NO:347), FIG. 244 (SEQ ID NO:349), FIG. 246 (SEQ ID NO:351),FIG. 248 (SEQ ID NO:353), FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ IDNO:357), FIG. 254 (SEQ ID NO:359), FIG. 256 (SEQ ID NO:361), FIG. 258(SEQ ID NO:363), FIG. 260 (SEQ ID NO:365), FIG. 262 (SEQ ID NO:367),FIG. 264 (SEQ ID NO:369), FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ IDNO:373), FIG. 270 (SEQ ID NO:375), FIG. 272 (SEQ ID NO:377), FIG. 274(SEQ ID NO:379), FIG. 276 (SEQ ID NO:381), FIG. 278 (SEQ ID NO:387),FIG. 280 (SEQ ID NO:389), FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ IDNO:399), FIG. 286 (SEQ ID NO:401), FIG. 288 (SEQ ID NO:403), FIG. 290(SEQ ID NO:408), FIG. 292 (SEQ ID NO:410), FIG. 294 (SEQ ID NO:412),FIG. 296 (SEQ ID NO:414), FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ IDNO:418), FIG. 302 (SEQ ID NO:420), FIG. 304 (SEQ ID NO:422), FIG. 306(SEQ ID NO:424), FIG. 308 (SEQ ID NO:495), FIG. 310 (SEQ ID NO:497),FIG. 32 (SEQ ID NO:499), FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ IDNO:503), FIG. 318 (SEQ ID NO:505), FIG. 320 (SEQ ID NO:507), FIG. 322(SEQ ID NO:509), FIG. 324 (SEQ ID NO:511), FIG. 326 (SEQ ID NO:513),FIG. 328 (SEQ ID NO:515) or FIG. 330 (SEQ ID NO:517), with itsassociated signal peptide; or (c) a nucleotide sequence encoding anextracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO:2),FIG. 4 (SEQ ID NO:6), FIG. 6 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:14), FIG.12 (SEQ ID NO:20), FIG. 15 (SEQ ID NO:23), FIG. 18 (SEQ ID NO:28), FIG.20 (SEQ ID NO:30), FIG. 23 (SEQ ID NO:33), FIG. 25 (SEQ ID NO:36), FIG.27 (SEQ ID NO:41), FIG. 30 (SEQ ID NO:47), FIG. 32 (SEQ ID NO:52), FIG.34 (SEQ ID NO:57), FIG. 36 (SEQ ID NO:62), FIG. 38 (SEQ ID NO:67), FIG.41 (SEQ ID NO:73), FIG. 47 (SEQ ID NO:84), FIG. 49 (SEQ ID NO:95), FIG.51 (SEQ ID NO:97), FIG. 53 (SEQ ID NO:99), FIG. 57 (SEQ ID NO:103), FIG.64 (SEQ ID NO:113), FIG. 66 (SEQ ID NO:115), FIG. 68 (SEQ ID NO:117),FIG. 70 (SEQ ID NO:119), FIG. 72 (SEQ ID NO:124), FIG. 74 (SEQ IDNO:129), FIG. 76 (SEQ ID NO:135), FIG. 79 (SEQ ID NO:138), FIG. 83 (SEQID NO:146), FIG. 85 (SEQ ID NO:148), FIG. 88 (SEQ ID NO:151), FIG. 90(SEQ ID NO:153), FIG. 93 (SEQ ID NO:156), FIG. 95 (SEQ ID NO:158), FIG.97 (SEQ ID NO:160), FIG. 99 (SEQ ID NO:165), FIG. 101 (SEQ ID NO:167),FIG. 103 (SEQ ID NO:169), FIG. 105 (SEQ ID NO:171), FIG. 109 (SEQ IDNO:175), FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ ID NO:179), FIG. 115(SEQ ID NO:181), FIG. 117 (SEQ ID NO:183), FIG. 120 (SEQ ID NO:189),FIG. 122 (SEQ ID NO:194), FIG. 125 (SEQ ID NO:197), FIG. 127 (SEQ IDNO:199), FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ ID NO:203), FIG. 133(SEQ ID NO:205), FIG. 135 (SEQ ID NO:207), FIG. 137 (SEQ ID NO:209),FIG. 139 (SEQ ID NO:211), FIG. 141 (SEQ ID NO:213), FIG. 144 (SEQ IDNO:216), FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ ID NO:221), FIG. 151(SEQ ID NO:223), FIG. 153 (SEQ ID NO:225), FIG. 155 (SEQ ID NO:227),FIG. 157 (SEQ ID NO:229), FIG. 159 (SEQ ID NO:231), FIG. 161 (SEQ IDNO:236), FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ ID NO:246), FIG. 167(SEQ ID NO:248), FIG. 169 (SEQ ID NO:250), FIG. 171 (SEQ ID NO:253),FIG. 174 (SEQ ID NO:256), FIG. 176 (SEQ ID NO:258), FIG. 178 (SEQ IDNO:260), FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ ID NO:264), FIG. 184(SEQ ID NO:266), FIG. 186 (SEQ ID NO:268), FIG. 188 (SEQ ID NO:270),FIG. 190 (SEQ ID NO:272), FIG. 192 (SEQ ID NO:274), FIG. 194 (SEQ IDNO:276), FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ ID NO:281), FIG. 200(SEQ ID NO:283), FIG. 202 (SEQ ID NO:285), FIG. 204 (SEQ ID NO:287),FIG. 206 (SEQ ID NO:289), FIG. 208 (SEQ ID NO:291), FIG. 210 (SEQ IDNO:293), FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ ID NO:297), FIG. 216(SEQ ID NO:299), FIG. 218 (SEQ ID NO:301), FIG. 220 (SEQ ID NO:303),FIG. 226 (SEQ ID NO:309), FIG. 228 (SEQ ID NO:314), FIG. 230 (SEQ IDNO:319), FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ ID NO:334), FIG. 238(SEQ ID NO:340), FIG. 240 (SEQ ID NO:345), FIG. 242 (SEQ ID NO:347),FIG. 244 (SEQ ID NO:349), FIG. 246 (SEQ ID NO:351), FIG. 248 (SEQ IDNO:353), FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ ID NO:357), FIG. 254(SEQ ID NO:359), FIG. 256 (SEQ ID NO:361), FIG. 258 (SEQ ID NO:363),FIG. 260 (SEQ ID NO:365), FIG. 262 (SEQ ID NO:367), FIG. 264 (SEQ IDNO:369), FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ ID NO:373), FIG. 270(SEQ ID NO:375), FIG. 272 (SEQ ID NO:377), FIG. 274 (SEQ ID NO:379),FIG. 276 (SEQ ID NO:381), FIG. 278 (SEQ ID NO:387), FIG. 280 (SEQ IDNO:389), FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ ID NO:399), FIG. 286(SEQ ID NO:401), FIG. 288 (SEQ ID NO:403), FIG. 290 (SEQ ID NO:408),FIG. 292 (SEQ ID NO:410), FIG. 294 (SEQ ID NO:412), FIG. 296 (SEQ IDNO:414), FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ ID NO:418), FIG. 302(SEQ ID NO:420), FIG. 304 (SEQ ID NO:422), FIG. 306 (SEQ ID NO:424),FIG. 308 (SEQ ID NO:495), FIG. 310 (SEQ ID NO:497), FIG. 312 (SEQ IDNO:499), FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ ID NO:503), FIG. 318(SEQ ID NO:505), FIG. 320 (SEQ ID NO:507), FIG. 322 (SEQ ID NO:509),FIG. 324 (SEQ ID NO:511), FIG. 326 (SEQ ID NO:513), FIG. 328 (SEQ IDNO:515) or FIG. 330 (SEQ ID NO:517), lacking its associated signalpeptide.
 28. An isolated polypeptide having at least 80% amino acidsequence identity to: (a) the polypeptide shown in FIG. 2 (SEQ ID NO:2),FIG. 4 (SEQ ID NO:6), FIG. 6 (SEQ ID NO:8), FIG. 9 (SEQ ID NO:14), FIG.12 (SEQ ID NO:20), FIG. 15 (SEQ ID NO:23), FIG. 18 (SEQ ID NO:28), FIG.20 (SEQ ID NO:30), FIG. 23 (SEQ ID NO:33), FIG. 25 (SEQ ID NO:36), FIG.27 (SEQ ID NO:41), FIG. 30 (SEQ ID NO:47), FIG. 32 (SEQ ID NO:52), FIG.34 (SEQ ID NO:57), FIG. 36 (SEQ ID NO:62), FIG. 38 (SEQ ID NO:67), FIG.41 (SEQ ID NO:73), FIG. 47 (SEQ ID NO:84), FIG. 49 (SEQ ID NO:95), FIG.51 (SEQ ID NO:97), FIG. 53 (SEQ ID NO:99), FIG. 57 (SEQ ID NO:103), FIG.64 (SEQ ID NO:113), FIG. 66 (SEQ ID NO:115), FIG. 68 (SEQ ID NO:117),FIG. 70 (SEQ ID NO:119), FIG. 72 (SEQ ID NO:124), FIG. 74 (SEQ IDNO:129), FIG. 76 (SEQ ID NO:135), FIG. 79 (SEQ ID NO:138), FIG. 83 (SEQID NO:146), FIG. 85 (SEQ ID NO:148), FIG. 88 (SEQ ID NO:151), FIG. 90(SEQ ID NO:153), FIG. 93 (SEQ ID NO:156), FIG. 95 (SEQ ID NO:158), FIG.97 (SEQ ID NO:160), FIG. 99 (SEQ ID NO:165), FIG. 101 (SEQ ID NO:167),FIG. 103 (SEQ ID NO:169), FIG. 105 (SEQ ID NO:171), FIG. 109 (SEQ IDNO:175), FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ ID NO:179), FIG. 115(SEQ ID NO:181), FIG. 117 (SEQ ID NO:183), FIG. 120 (SEQ ID NO:189),FIG. 122 (SEQ ID NO:194), FIG. 125 (SEQ ID NO:197), FIG. 127 (SEQ IDNO:199), FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ ID NO:203), FIG. 133(SEQ ID NO:205), FIG. 135 (SEQ ID NO:207), FIG. 137 (SEQ ID NO:209),FIG. 139 (SEQ ID NO:211), FIG. 141 (SEQ ID NO:213), FIG. 144 (SEQ IDNO:216), FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ ID NO:221), FIG. 151(SEQ ID NO:223), FIG. 153 (SEQ ID NO:225), FIG. 155 (SEQ ID NO:227),FIG. 157 (SEQ ID NO:229), FIG. 159 (SEQ ID NO:231), FIG. 161 (SEQ IDNO:236), FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ ID NO:246), FIG. 167(SEQ ID NO:248), FIG. 169 (SEQ ID NO:250), FIG. 171 (SEQ ID NO:253),FIG. 174 (SEQ ID NO:256), FIG. 176 (SEQ ID NO:258), FIG. 178 (SEQ IDNO:260), FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ ID NO:264), FIG. 184(SEQ ID NO:266), FIG. 186 (SEQ ID NO:268), FIG. 188 (SEQ ID NO:270),FIG. 190 (SEQ ID NO:272), FIG. 192 (SEQ ID NO:274), FIG. 194 (SEQ IDNO:276), FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ ID NO:281), FIG. 200(SEQ ID NO:283), FIG. 202 (SEQ ID NO:285), FIG. 204 (SEQ ID NO:287),FIG. 206 (SEQ ID NO:289), FIG. 208 (SEQ ID NO:291), FIG. 210 (SEQ IDNO:293), FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ ID NO:297), FIG. 216(SEQ ID NO:299), FIG. 218 (SEQ ID NO:301), FIG. 220 (SEQ ID NO:303),FIG. 226 (SEQ ID NO:309), FIG. 228 (SEQ ID NO:314), FIG. 230 (SEQ IDNO:319), FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ ID NO:334), FIG. 238(SEQ ID NO:340), FIG. 240 (SEQ ID NO:345), FIG. 242 (SEQ ID NO:347),FIG. 244 (SEQ ID NO:349), FIG. 246 (SEQ ID NO:351), FIG. 248 (SEQ IDNO:353), FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ ID NO:357), FIG. 254(SEQ ID NO:359), FIG. 256 (SEQ ID NO:361), FIG. 258 (SEQ ID NO:363),FIG. 260 (SEQ ID NO:365), FIG. 262 (SEQ ID NO:367), FIG. 264 (SEQ IDNO:369), FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ ID NO:373), FIG. 270(SEQ ID NO:375), FIG. 272 (SEQ ID NO:377), FIG. 274 (SEQ ID NO:379),FIG. 276 (SEQ ID NO:381), FIG. 278 (SEQ ID NO:387), FIG. 280 (SEQ IDNO:389), FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ ID NO:399), FIG. 286(SEQ ID NO:401), FIG. 288 (SEQ ID NO:403), FIG. 290 (SEQ ID NO:408),FIG. 292 (SEQ ID NO:410), FIG. 294 (SEQ ID NO:412), FIG. 296 (SEQ IDNO:414), FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ ID NO:418), FIG. 302(SEQ ID NO:420), FIG. 304 (SEQ ID NO:422), FIG. 306 (SEQ ID NO:424),FIG. 308 (SEQ ID NO:495), FIG. 310 (SEQ ID NO:497), FIG. 312 (SEQ IDNO:499), FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ ID NO:503), FIG. 318(SEQ ID NO:505), FIG. 320 (SEQ ID NO:507), FIG. 322 (SEQ ID NO:509),FIG. 324 (SEQ ID NO:511), FIG. 326 (SEQ ID NO:513), FIG. 328 (SEQ IDNO:515) or FIG. 330 (SEQ ID NO:517), lacking its associated signalpeptide; (b) an extracellular domain of the polypeptide shown in FIG. 2(SEQ ID NO:2), FIG. 4 (SEQ ID NO:6), FIG. 6 (SEQ ID NO:8), FIG. 9 (SEQID NO:14), FIG. 12 (SEQ ID NO:20), FIG. 15 (SEQ ID NO:23), FIG. 18 (SEQID NO:28), FIG. 20 (SEQ ID NO:30), FIG. 23 (SEQ ID NO:33), FIG. 25 (SEQID NO:36), FIG. 27 (SEQ ID NO:41), FIG. 30 (SEQ ID NO:47), FIG. 32 (SEQID NO:52), FIG. 34 (SEQ ID NO:57), FIG. 36 (SEQ ID NO:62), FIG. 38 (SEQID NO:67), FIG. 41 (SEQ ID NO:73), FIG. 47 (SEQ ID NO:84), FIG. 49 (SEQID NO:95), FIG. 51 (SEQ ID NO:97), FIG. 53 (SEQ ID NO:99), FIG. 57 (SEQID NO:103), FIG. 64 (SEQ ID NO:113), FIG. 66 (SEQ ID NO:115), FIG. 68(SEQ ID NO:117), FIG. 70 (SEQ ID NO:119), FIG. 72 (SEQ ID NO:124), FIG.74 (SEQ ID NO:129), FIG. 76 (SEQ ID NO:135), FIG. 79 (SEQ ID NO:138),FIG. 83 (SEQ ID NO:146), FIG. 85 (SEQ ID NO:148), FIG. 88 (SEQ IDNO:151), FIG. 90 (SEQ ID NO:153), FIG. 93 (SEQ ID NO:156), FIG. 95 (SEQID NO:158), FIG. 97 (SEQ ID NO:160), FIG. 99 (SEQ ID NO:165), FIG. 101(SEQ ID NO:167), FIG. 103 (SEQ ID NO:169), FIG. 105 (SEQ ID NO:171),FIG. 109 (SEQ ID NO:175), FIG. 111 (SEQ ID NO:177), FIG. 113 (SEQ IDNO:179), FIG. 115 (SEQ ID NO:181), FIG. 117 (SEQ ID NO:183), FIG. 120(SEQ ID NO:189), FIG. 122 (SEQ ID NO:194), FIG. 125 (SEQ ID NO:197),FIG. 127 (SEQ ID NO:199), FIG. 129 (SEQ ID NO:201), FIG. 131 (SEQ IDNO:203), FIG. 133 (SEQ ID NO:205), FIG. 135 (SEQ ID NO:207), FIG. 137(SEQ ID NO:209), FIG. 139 (SEQ ID NO:211), FIG. 141 (SEQ ID NO:213),FIG. 144 (SEQ ID NO:216), FIG. 147 (SEQ ID NO:219), FIG. 149 (SEQ IDNO:221), FIG. 151 (SEQ ID NO:223), FIG. 153 (SEQ ID NO:225), FIG. 155(SEQ ID NO:227), FIG. 157 (SEQ ID NO:229), FIG. 159 (SEQ ID NO:231),FIG. 161 (SEQ ID NO:236), FIG. 163 (SEQ ID NO:241), FIG. 165 (SEQ IDNO:246), FIG. 167 (SEQ ID NO:248), FIG. 169 (SEQ ID NO:250), FIG. 171(SEQ ID NO:253), FIG. 174 (SEQ ID NO:256), FIG. 176 (SEQ ID NO:258),FIG. 178 (SEQ ID NO:260), FIG. 180 (SEQ ID NO:262), FIG. 182 (SEQ IDNO:264), FIG. 184 (SEQ ID NO:266), FIG. 186 (SEQ ID NO:268), FIG. 188(SEQ ID NO:270), FIG. 190 (SEQ ID NO:272), FIG. 192 (SEQ ID NO:274),FIG. 194 (SEQ ID NO:276), FIG. 196 (SEQ ID NO:278), FIG. 198 (SEQ IDNO:281), FIG. 200 (SEQ ID NO:283), FIG. 202 (SEQ ID NO:285), FIG. 204(SEQ ID NO:287), FIG. 206 (SEQ ID NO:289), FIG. 208 (SEQ ID NO:291),FIG. 210 (SEQ ID NO:293), FIG. 212 (SEQ ID NO:295), FIG. 214 (SEQ IDNO:297), FIG. 216 (SEQ ID NO:299), FIG. 218 (SEQ ID NO:301), FIG. 220(SEQ ID NO:303), FIG. 226 (SEQ ID NO:309), FIG. 228 (SEQ ID NO:314),FIG. 230 (SEQ ID NO:319), FIG. 233 (SEQ ID NO:326), FIG. 235 (SEQ IDNO:334), FIG. 238 (SEQ ID NO:340), FIG. 240 (SEQ ID NO:345), FIG. 242(SEQ ID NO:347), FIG. 244 (SEQ ID NO:349), FIG. 246 (SEQ ID NO:351),FIG. 248 (SEQ ID NO:353), FIG. 250 (SEQ ID NO:355), FIG. 252 (SEQ IDNO:357), FIG. 254 (SEQ ID NO:359), FIG. 256 (SEQ ID NO:361), FIG. 258(SEQ ID NO:363), FIG. 260 (SEQ ID NO:365), FIG. 262 (SEQ ID NO:367),FIG. 264 (SEQ ID NO:369), FIG. 266 (SEQ ID NO:371), FIG. 268 (SEQ IDNO:373), FIG. 270 (SEQ ID NO:375), FIG. 272 (SEQ ID NO:377), FIG. 274(SEQ ID NO:379), FIG. 276 (SEQ ID NO:381), FIG. 278 (SEQ ID NO:387),FIG. 280 (SEQ ID NO:389), FIG. 282 (SEQ ID NO:394), FIG. 284 (SEQ IDNO:399), FIG. 286 (SEQ ID NO:401), FIG. 288 (SEQ ID NO:403), FIG. 290(SEQ ID NO:408), FIG. 292 (SEQ ID NO:410), FIG. 294 (SEQ ID NO:412),FIG. 296 (SEQ ID NO:414), FIG. 298 (SEQ ID NO:416), FIG. 300 (SEQ IDNO:418), FIG. 302 (SEQ ID NO:420), FIG. 304 (SEQ ID NO:422), FIG. 306(SEQ ID NO:424), FIG. 308 (SEQ ID NO:495), FIG. 310 (SEQ ID NO:497),FIG. 312 (SEQ ID NO:499), FIG. 314 (SEQ ID NO:501), FIG. 316 (SEQ IDNO:503), FIG. 318 (SEQ ID NO:505), FIG. 320 (SEQ ID NO:507), FIG. 322(SEQ ID NO:509), FIG. 324 (SEQ ID NO:511), FIG. 326 (SEQ ID NO:513),FIG. 328 (SEQ ID NO:515) or FIG. 330 (SEQ ID NO:517), with itsassociated signal peptide; or (c) an extracellular domain of thepolypeptide shown in FIG. 2 (SEQ ID NO:2), FIG. 4 (SEQ ID NO:6), FIG. 6(SEQ ID NO:8), FIG. 9 (SEQ ID NO:14), FIG. 12 (SEQ ID NO:20), FIG. 15(SEQ ID NO:23), FIG. 18 (SEQ ID NO:28), FIG. 20 (SEQ ID NO:30), FIG. 23(SEQ ID NO:33), FIG. 25 (SEQ ID NO:36), FIG. 27 (SEQ ID NO:41), FIG. 30(SEQ ID NO:47), FIG. 32 (SEQ ID NO:52), FIG. 34 (SEQ ID NO:57), FIG. 36(SEQ ID NO:62), FIG. 38 (SEQ ID NO:67), FIG. 41 (SEQ ID NO:73), FIG. 47(SEQ ID NO:84), FIG. 49 (SEQ ID NO:95), FIG. 51 (SEQ ID NO:97), FIG. 53(SEQ ID NO:99), FIG. 57 (SEQ ID NO:103), FIG. 64 (SEQ ID NO:113), FIG.66 (SEQ ID NO:115), FIG. 68 (SEQ ID NO:117), FIG. 70 (SEQ ID NO:119),FIG. 72 (SEQ ID NO:124), FIG. 74 (SEQ ID NO:129), FIG. 76 (SEQ IDNO:135), FIG. 79 (SEQ ID NO:138), FIG. 83 (SEQ ID NO:146), FIG. 85 (SEQID NO:148), FIG. 88 (SEQ ID NO:151), FIG. 90 (SEQ ID NO:153), FIG. 93(SEQ ID NO:156), FIG. 95 (SEQ ID NO:158), FIG. 97 (SEQ ID NO:160), FIG.99 (SEQ ID NO:165), FIG. 101 (SEQ ID NO:167), FIG. 103 (SEQ ID NO:169),FIG. 105 (SEQ ID NO:171), FIG. 109 (SEQ ID NO:175), FIG. 111 (SEQ IDNO:177), FIG. 113 (SEQ ID NO:179), FIG. 115 (SEQ ID NO:181), FIG. 117(SEQ ID NO:183), FIG. 120 (SEQ ID NO:189), FIG. 122 (SEQ ID NO:194),FIG. 125 (SEQ ID NO:197), FIG. 127 (SEQ ID NO:199), FIG. 129 (SEQ IDNO:201), FIG. 131 (SEQ ID NO:203), FIG. 133 (SEQ ID NO:205), FIG. 135(SEQ ID NO:207), FIG. 137 (SEQ ID NO:209), FIG. 139 (SEQ ID NO:211),FIG. 141 (SEQ ID NO:213), FIG. 144 (SEQ ID NO:216), FIG. 147 (SEQ IDNO:219), FIG. 149 (SEQ ID NO:221), FIG. 151 (SEQ ID NO:223), FIG. 153(SEQ ID NO:225), FIG. 155 (SEQ ID NO:227), FIG. 157 (SEQ ID NO:229),FIG. 159 (SEQ ID NO:231), FIG. 161 (SEQ ID NO:236), FIG. 163 (SEQ IDNO:241), FIG. 165 (SEQ ID NO:246), FIG. 167 (SEQ ID NO:248), FIG. 169(SEQ ID NO:250), FIG. 171 (SEQ ID NO:253), FIG. 174 (SEQ ID NO:256),FIG. 176 (SEQ ID NO:258), FIG. 178 (SEQ ID NO:260), FIG. 180 (SEQ IDNO:262), FIG. 182 (SEQ ID NO:264), FIG. 184 (SEQ ID NO:266), FIG. 186(SEQ ID NO:268), FIG. 188 (SEQ ID NO:270), FIG. 190 (SEQ ID NO:272),FIG. 192 (SEQ ID NO:274), FIG. 194 (SEQ ID NO:276), FIG. 196 (SEQ IDNO:278), FIG. 198 (SEQ ID NO:281), FIG. 200 (SEQ ID NO:283), FIG. 202(SEQ ID NO:285), FIG. 204 (SEQ ID NO:287), FIG. 206 (SEQ ID NO:289),FIG. 208 (SEQ ID NO:291), FIG. 210 (SEQ ID NO:293), FIG. 212 (SEQ IDNO:295), FIG. 214 (SEQ ID NO:297), FIG. 216 (SEQ ID NO:299), FIG. 218(SEQ ID NO:301), FIG. 220 (SEQ ID NO:303), FIG. 226 (SEQ ID NO:309),FIG. 228 (SEQ ID NO:314), FIG. 230 (SEQ ID NO:319), FIG. 233 (SEQ IDNO:326), FIG. 235 (SEQ ID NO:334), FIG. 238 (SEQ ID NO:340), FIG. 240(SEQ ID NO:345), FIG. 242 (SEQ ID NO:347), FIG. 244 (SEQ ID NO:349),FIG. 246 (SEQ ID NO:351), FIG. 248 (SEQ ID NO:353), FIG. 250 (SEQ IDNO:355), FIG. 252 (SEQ ID NO:357), FIG. 254 (SEQ ID NO:359), FIG. 256(SEQ ID NO:361), FIG. 258 (SEQ ID NO:363), FIG. 260 (SEQ ID NO:365),FIG. 262 (SEQ ID NO:367), FIG. 264 (SEQ ID NO:369), FIG. 266 (SEQ IDNO:371), FIG. 268 (SEQ ID NO:373), FIG. 270 (SEQ ID NO:375), FIG. 272(SEQ ID NO:377), FIG. 274 (SEQ ID NO:379), FIG. 276 (SEQ ID NO:381),FIG. 278 (SEQ ID NO:387), FIG. 280 (SEQ ID NO:389), FIG. 282 (SEQ IDNO:394), FIG. 284 (SEQ ID NO:399), FIG. 286 (SEQ ID NO:401), FIG. 288(SEQ ID NO:403), FIG. 290 (SEQ ID NO:408), FIG. 292 (SEQ ID NO:410),FIG. 294 (SEQ ID NO:412), FIG. 296 (SEQ ID NO:414), FIG. 298 (SEQ IDNO:416), FIG. 300 (SEQ ID NO:418), FIG. 302 (SEQ ID NO:420), FIG. 304(SEQ ID NO:422), FIG. 306 (SEQ ID NO:424), FIG. 308 (SEQ ID NO:495),FIG. 310 (SEQ ID NO:497), FIG. 312 (SEQ ID NO:499), FIG. 314 (SEQ IDNO:501), FIG. 316 (SEQ ID NO:503), FIG. 318 (SEQ ID NO:505), FIG. 320(SEQ ID NO:507), FIG. 322 (SEQ ID NO:509), FIG. 324 (SEQ ID NO:511),FIG. 326 (SEQ ID NO:513), FIG. 328 (SEQ ID NO:515) or FIG. 330 (SEQ IDNO:517), lacking its associated signal peptide.
 29. A method ofdetecting a PRO943 polypeptide in a sample suspected of containing aPRO943 polypeptide, said method comprising contacting said sample with aPRO183, PRO184 or PRO185 polypeptide and determining the formation of aPRO943/PRO183, PRO184 or PRO185 polypeptide conjugate in said sample,wherein the formation of said conjugate is indicative of the presence ofa PRO943 polypeptide in said sample.
 30. The method according to claim29, wherein said sample comprises cells suspected of expressing saidPRO943 polypeptide.
 31. The method according to claim 29, wherein saidPRO183, PRO184 or PRO185 polypeptide is labeled with a detectable label.32. The method according to claim 29, wherein said PRO183, PRO184 orPRO185 polypeptide is attached to a solid support.
 33. A method ofdetecting a PRO183, PRO184 or PRO185 polypeptide in a sample suspectedof containing a PRO183, PRO184 or PRO185 polypeptide, said methodcomprising contacting said sample with a PRO943 polypeptide anddetermining the formation of a PRO943/PRO183, PRO184 or PRO185polypeptide conjugate in said sample, wherein the formation of saidconjugate is indicative of the presence of a PRO183, PRO184 or PRO185polypeptide in said sample.
 34. The method according to claim 33,wherein said sample comprises cells suspected of expressing said PRO183,PRO184 or PRO185 polypeptide.
 35. The method according to claim 33,wherein said PRO943 polypeptide is labeled with a detectable label. 36.The method according to claim 33, wherein said PRO943 polypeptide isattached to a solid support.
 37. A method of detecting a PRO331polypeptide in a sample suspected of containing a PRO331 polypeptide,said method comprising contacting said sample with a PRO1133 polypeptideand determining the formation of a PRO331/PRO1133 polypeptide conjugatein said sample, wherein the formation of said conjugate is indicative ofthe presence of a PRO331 polypeptide in said sample.
 38. The methodaccording to claim 37, wherein said sample comprises cells suspected ofexpressing said PRO331 polypeptide.
 39. The method according to claim37, wherein said PRO1133 polypeptide is labeled with a detectable label.40. The method according to claim 37, wherein said PRO1133 polypeptideis attached to a solid support.
 41. A method of detecting a PRO1133polypeptide in a sample suspected of containing a PRO1133 polypeptide,said method comprising contacting said sample with a PRO331 polypeptideand determining the formation of a PRO331/PRO1133 polypeptide conjugatein said sample, wherein the formation of said conjugate is indicative ofthe presence of a PRO1133 polypeptide in said sample.
 42. The methodaccording to claim 41, wherein said sample comprises cells suspected ofexpressing said PRO1133 polypeptide.
 43. The method according to claim41, wherein said PRO331 polypeptide is labeled with a detectable label.44. The method according to claim 41, wherein said PRO331 polypeptide isattached to a solid support.
 45. A method of detecting a PRO363 orPRO5723 polypeptide in a sample suspected of containing a PRO363 orPRO5723 polypeptide, said method comprising contacting said sample witha PRO1387 polypeptide and determining the formation of a PRO363 orPRO5723/PRO1387 polypeptide conjugate in said sample, wherein theformation of said conjugate is indicative of the presence of a PRO363 orPRO5723 polypeptide in said sample.
 46. The method according to claim45, wherein said sample comprises cells suspected of expressing saidPRO363 or PRO5723 polypeptide.
 47. The method according to claim 45,wherein said PRO1387 polypeptide is labeled with a detectable label. 48.The method according to claim 45, wherein said PRO1387 polypeptide isattached to a solid support.
 49. A method of detecting a PRO1387polypeptide in a sample suspected of containing a PRO1387 polypeptide,said method comprising contacting said sample with a PRO363 or PRO5723polypeptide and determining the formation of a PRO363 or PRO5723/PRO1387polypeptide conjugate in said sample, wherein the formation of saidconjugate is indicative of the presence of a PRO1387 polypeptide in saidsample.
 50. The method according to claim 49, wherein said samplecomprises cells suspected of expressing said PRO1387 polypeptide. 51.The method according to claim 49, wherein said PRO363 or PRO5723polypeptide is labeled with a detectable label.
 52. The method accordingto claim 49, wherein said PRO363 or PRO5723 polypeptide is attached to asolid support.
 53. A method of detecting a PRO1114 polypeptide in asample suspected of containing a PRO1114 polypeptide, said methodcomprising contacting said sample with a PRO3301 or PRO9940 polypeptideand determining the formation of a PRO1114/PRO3301 or PRO9940polypeptide conjugate in said sample, wherein the formation of saidconjugate is indicative of the presence of a PRO1114 polypeptide in saidsample.
 54. The method according to claim 53, wherein said samplecomprises cells suspected of expressing said PRO1114 polypeptide. 55.The method according to claim 53, wherein said PRO3301 or PRO9940polypeptide is labeled with a detectable label.
 56. The method accordingto claim 53, wherein said PRO3301 or PRO9940 polypeptide is attached toa solid support.
 57. A method of detecting a PRO3301 or PRO9940polypeptide in a sample suspected of containing a PRO3301 or PRO9940polypeptide, said method comprising contacting said sample with aPRO1114 polypeptide and determining the formation of a PRO3301 orPRO9940/PRO1114 polypeptide conjugate in said sample, wherein theformation of said conjugate is indicative of the presence of a PRO3301or PRO9940 polypeptide in said sample.
 58. The method according to claim57, wherein said sample comprises cells suspected of expressing saidPRO3301 or PRO9940 polypeptide.
 59. The method according to claim 57,wherein said PRO1114 polypeptide is labeled with a detectable label. 60.The method according to claim 57, wherein said PRO1114 polypeptide isattached to a solid support.
 61. A method of detecting a PRO1181polypeptide in a sample suspected of containing a PRO1181 polypeptide,said method comprising contacting said sample with a PRO7170, PRO361 orPRO846 polypeptide and determining the formation of a PRO1181/PRO7170,PRO361 or PRO846 polypeptide conjugate in said sample, wherein theformation of said conjugate is indicative of the presence of a PRO1181polypeptide in said sample.
 62. The method according to claim 61,wherein said sample comprises cells suspected of expressing said PRO1181polypeptide.
 63. The method according to claim 61, wherein said PRO7170,PRO361 or PRO846 polypeptide is labeled with a detectable label.
 64. Themethod according to claim 61, wherein said PRO7170, PRO361 or PRO846polypeptide is attached to a solid support.
 65. A method of detecting aPRO7170, PRO361 or PRO846 polypeptide in a sample suspected ofcontaining a PRO7170, PRO361 or PRO846 polypeptide, said methodcomprising contacting said sample with a PRO1181 polypeptide anddetermining the formation of a PRO1181/PRO7170, PRO361 or PRO846polypeptide conjugate in said sample, wherein the formation of saidconjugate is indicative of the presence of a PRO7170, PRO361 or PRO846polypeptide in said sample.
 66. The method according to claim 65,wherein said sample comprises cells suspected of expressing saidPRO7170, PRO361 or PRO846 polypeptide.
 67. The method according to claim65, wherein said PRO1181 polypeptide is labeled with a detectable label.68. The method according to claim 65, wherein said PRO1181 polypeptideis attached to a solid support.
 69. A method of linking a bioactivemolecule to a cell expressing a PRO943 polypeptide, said methodcomprising contacting said cell with a PRO183, PRO184 or PRO185polypeptide that is bound to said bioactive molecule and allowing saidPRO943 and PRO183, PRO184 or PRO185 polypeptides to bind to one another,thereby linking said bioactive molecules to said cell.
 70. The methodaccording to claim 69, wherein said bioactive molecule is a toxin, aradiolabel or an antibody.
 71. The method according to claim 69, whereinsaid bioactive molecule causes the death of said cell.
 72. A method oflinking a bioactive molecule to a cell expressing a PRO183, PRO184 orPRO185 polypeptide, said method comprising contacting said cell with aPRO943 polypeptide that is bound to said bioactive molecule and allowingsaid PRO943 and PRO183, PRO184 or PRO185 polypeptides to bind to oneanother, thereby linking said bioactive molecules to said cell.
 73. Themethod according to claim 72, wherein said bioactive molecule is atoxin, a radiolabel or an antibody.
 74. The method according to claim73, wherein said bioactive molecule causes the death of said cell.
 75. Amethod of linking a bioactive molecule to a cell expressing a PRO331polypeptide, said method comprising contacting said cell with a PRO1133polypeptide that is bound to said bioactive molecule and allowing saidPRO331 and PRO1133 polypeptides to bind to one another, thereby linkingsaid bioactive molecules to said cell.
 76. The method according to claim75, wherein said bioactive molecule is a toxin, a radiolabel or anantibody.
 77. The method according to claim 75, wherein said bioactivemolecule causes the death of said cell.
 78. A method of linking abioactive molecule to a cell expressing a PRO1133 polypeptide, saidmethod comprising contacting said cell with a PRO331 polypeptide that isbound to said bioactive molecule and allowing said PRO331 and PRO1133polypeptides to bind to one another, thereby linking said bioactivemolecules to said cell.
 79. The method according to claim 78, whereinsaid bioactive molecule is a toxin, a radiolabel or an antibody.
 80. Themethod according to claim 78, wherein said bioactive molecule causes thedeath of said cell.
 81. A method of linking a bioactive molecule to acell expressing a PRO1387 polypeptide, said method comprising contactingsaid cell with a PRO363 or PRO5723 polypeptide that is bound to saidbioactive molecule and allowing said PRO1387 and PRO363 or PRO5723polypeptides to bind to one another, thereby linking said bioactivemolecules to said cell.
 82. The method according to claim 81, whereinsaid bioactive molecule is a toxin, a radiolabel or an antibody.
 83. Themethod according to claim 81, wherein said bioactive molecule causes thedeath of said cell.
 84. A method of linking a bioactive molecule to acell expressing a PRO363 or PRO5723 polypeptide, said method comprisingcontacting said cell with a PRO1387 polypeptide that is bound to saidbioactive molecule and allowing said PRO1387 and PRO363 or PRO5723polypeptides to bind to one another, thereby linking said bioactivemolecules to said cell.
 85. The method according to claim 84, whereinsaid bioactive molecule is a toxin, a radiolabel or an antibody.
 86. Themethod according to claim 84, wherein said bioactive molecule causes thedeath of said cell.
 87. A method of linking a bioactive molecule to acell expressing a PRO1114 polypeptide, said method comprising contactingsaid cell with a PRO3301 or PRO9940 polypeptide that is bound to saidbioactive molecule and allowing said PRO1114 and PRO3301 or PRO9940polypeptides to bind to one another, thereby linking said bioactivemolecules to said cell.
 88. The method according to claim 87, whereinsaid bioactive molecule is a toxin, a radiolabel or an antibody.
 89. Themethod according to claim 87, wherein said bioactive molecule causes thedeath of said cell.
 90. A method of linking a bioactive molecule to acell expressing a PRO3301 or PRO9940 polypeptide, said method comprisingcontacting said cell with a PRO1114 polypeptide that is bound to saidbioactive molecule and allowing said PRO1114 and PRO3301 or PRO9940polypeptides to bind to one another, thereby linking said bioactivemolecules to said cell.
 91. The method according to claim 90, whereinsaid bioactive molecule is a toxin, a radiolabel or an antibody.
 92. Themethod according to claim 90, wherein said bioactive molecule causes thedeath of said cell.
 93. A method of linking a bioactive molecule to acell expressing a PRO1181 polypeptide, said method comprising contactingsaid cell with a PRO7170, PRO361 or PRO846 polypeptide that is bound tosaid bioactive molecule and allowing said PRO1181 and PRO7170, PRO361 orPRO846 polypeptides to bind to one another, thereby linking saidbioactive molecules to said cell.
 94. The method according to claim 93,wherein said bioactive molecule is a toxin, a radiolabel or an antibody.95. The method according to claim 93, wherein said bioactive moleculecauses the death of said cell.
 96. A method of linking a bioactivemolecule to a cell expressing a PRO7170, PRO361 or PRO846 polypeptide,said method comprising contacting said cell with a PRO1181 polypeptidethat is bound to said bioactive molecule and allowing said PRO1181 andPRO7170, PRO361 or PRO846 polypeptides to bind to one another, therebylinking said bioactive molecules to said cell.
 97. The method accordingto claim 96, wherein said bioactive molecule is a toxin, a radiolabel oran antibody.
 98. The method according to claim 96, wherein saidbioactive molecule causes the death of said cell.
 99. A method ofmodulating at least one biological activity of a cell expressing aPRO943 polypeptide, said method comprising contacting said cell with aPRO183, PRO184 or PRO185 polypeptide or an anti-PRO943 antibody, wherebysaid PRO183, PRO184 or PRO185 polypeptide or said anti-PRO943 antibodybinds to said PRO943 polypeptide, thereby modulating at least onebiological activity of said cell.
 100. The method according to claim 99,wherein said cell is killed.
 101. A method of modulating at least onebiological activity of a cell expressing a PRO183, PRO184 or PRO185polypeptide, said method comprising contacting said cell with a PRO943polypeptide or an anti-PRO183, anti-PRO184 or anti-PRO185 antibody,whereby said PRO943 polypeptide or said anti-PRO183, anti-PRO184 oranti-PRO185 antibody binds to said PRO183, PRO184 or PRO185 polypeptide,thereby modulating at least one biological activity of said cell. 102.The method according to claim 101, wherein said cell is killed.
 103. Amethod of modulating at least one biological activity of a cellexpressing a PRO331 polypeptide, said method comprising contacting saidcell with a PRO1133 polypeptide or an anti-PRO331 antibody, whereby saidPRO1133 polypeptide or said anti-PRO331 antibody binds to said PRO331polypeptide, thereby modulating at least one biological activity of saidcell.
 104. The method according to claim 103, wherein said cell iskilled.
 105. A method of modulating at least one biological activity ofa cell expressing a PRO1133 polypeptide, said method comprisingcontacting said cell with a PRO331 polypeptide or an anti-PRO1133antibody, whereby said PRO331 polypeptide or said anti-PRO1133 antibodybinds to said PRO1133 polypeptide, thereby modulating at least onebiological activity of said cell.
 106. The method according to claim105, wherein said cell is killed.
 107. A method of modulating at leastone biological activity of a cell expressing a PRO1387 polypeptide, saidmethod comprising contacting said cell with a PRO363 or PRO5723polypeptide or an anti-PRO1387 antibody, whereby said PRO363 or PRO5723polypeptide or said anti-PRO1387 antibody binds to said PRO1387polypeptide, thereby modulating at least one biological activity of saidcell.
 108. The method according to claim 107, wherein said cell iskilled.
 109. A method of modulating at least one biological activity ofa cell expressing a PRO363 or PRO5723 polypeptide, said methodcomprising contacting said cell with a PRO1387 polypeptide or ananti-PRO363 or anti-PRO5723 antibody, whereby said PRO1387 polypeptideor said anti-PRO363 or anti-PRO5723 antibody binds to said PRO363 orPRO5723 polypeptide, thereby modulating at least one biological activityof said cell.
 110. The method according to claim 109, wherein said cellis killed.
 111. A method of modulating at least one biological activityof a cell expressing a PRO1114 polypeptide, said method comprisingcontacting said cell with a PRO3301 or PRO9940 polypeptide or ananti-PRO1114 antibody, whereby said PRO3301 or PRO9940 polypeptide orsaid anti-PRO1114 antibody binds to said PRO1114 polypeptide, therebymodulating at least one biological activity of said cell.
 112. Themethod according to claim 111, wherein said cell is killed.
 113. Amethod of modulating at least one biological activity of a cellexpressing a PRO3301 or PRO9940 polypeptide, said method comprisingcontacting said cell with a PRO1114 polypeptide or an anti-PRO3301 oranti-PRO9940 antibody, whereby said PRO1114 polypeptide or saidanti-PRO3301 or anti-PRO9940 antibody binds to said PRO3301 or PRO9940polypeptide, thereby modulating at least one biological activity of saidcell.
 114. The method according to claim 113, wherein said cell iskilled.
 115. A method of modulating at least one biological activity ofa cell expressing a PRO1181 polypeptide, said method comprisingcontacting said cell with a PRO7170, PRO361 or PRO846 polypeptide or ananti-PRO1181 antibody, whereby said PRO7170, PRO361 or PRO846polypeptide or said anti-PRO1181 antibody binds to said PRO1181polypeptide, thereby modulating at least one biological activity of saidcell.
 116. The method according to claim 115, wherein said cell iskilled.
 117. A method of modulating at least one biological activity ofa cell expressing a PRO7170, PRO361 or PRO846 polypeptide, said methodcomprising contacting said cell with a PRO1181 polypeptide or ananti-PRO7170, anti-PRO361 or anti-PRO846 antibody, whereby said PRO1181polypeptide or said anti-PRO7170, anti-PRO361 or anti-PRO846 antibodybinds to said PRO7170, PRO361 or PRO846 polypeptide, thereby modulatingat least one biological activity of said cell.
 118. The method accordingto claim 117, wherein said cell is killed.